Pan Yang; Hui-juan Mei; Hao-yu Zhao; Rong-rong Wu; Yong-qin Ge; Yin Lu

doi:10.4040/jkan.24041

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Review Paper
Exploring Symptom Cluster Patterns in Adult Cancer Patients Undergoing Chemotherapy: A Systematic Review: Pan Yang^1,2,*, Hui-juan Mei^1,2,*, Hao-yu Zhao^1,2, Rong-rong Wu^1,2, Yong-qin Ge¹, Yin Lu¹; Journal of Korean Academy of Nursing 2024;54(4):478-494.
DOI: https://doi.org/10.4040/jkan.24041
Published online: November 25, 2024

¹Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China

²Suzhou Medical College of Soochow University, Suzhou, China

Address reprint requests to : Lu, Yin Department of Hematology, First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Gusu District, Suzhou 215000, China Tel: +86-177-1266-1310 Fax: +86-6-778-0942 E-mail: luyin@suda.edu.cn

Ge, Yong-qin Department of Hematology, First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Gusu District, Suzhou 215000, China Tel: +86-139-6218-6063 Fax: +86-6-778-0322 E-mail: geyongqin@suda.edu.cn

*These authors contributed equally as first authors.

• Received: March 20, 2024 • Revised: May 20, 2024 • Accepted: September 21, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution NoDerivs License (http://creativecommons.org/licenses/by-nd/4.0) If the original work is properly cited and retained without any modification or reproduction, it can be used and re-distributed in any format and medium.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
CONCLUSION
Article Information
SUPPLEMENTARY DATA
References

Abstract

Purpose
This systematic review aimed to scrutinize the progression of symptom cluster research in adult cancer patients who received primary or adjuvant chemotherapy between 2001 and 2023, providing a comprehensive understanding of clinical practice and future research.
Methods
PubMed, Ovid MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Web of Science databases were searched for theme words and free words related to symptom clusters, cancer, and chemotherapy. Eligible studies were published between January 1, 2001, and May 30, 2023; adults who were diagnosed with cancer and received primary or adjuvant chemotherapy were evaluated.
Results
Twenty-eight studies were included in this review. The Memorial Symptom Assessment Scale emerged as the predominant instrument and exploratory factor analysis was the most frequently employed statistical method to identify symptom clusters. Psychological, gastrointestinal, and physical image symptom clusters were the most commonly delineated. Furthermore, the temporal stability of the symptom clusters showed varying dynamics, with psychological symptom clusters displaying relative consistency over time.
Conclusion
Interventions are needed for the most common and stable symptoms in patients with cancer undergoing chemotherapy. Future endeavors may necessitate more longitudinal studies to delve deeper into the temporal stability and dynamic variations of symptom clusters. Such investigations hold promise for advancing symptom cluster research, elucidating the underlying mechanisms, and fostering the development of targeted interventions, thereby enriching the symptom management paradigm in oncological care.
Key words: Symptom Cluster; Chemotherapy; Cancer

INTRODUCTION

Cancer morbidity and mortality are increasing and have become a significant global burden [1]. There were 19.3 million new cancer cases and nearly 10 million cancer-related deaths in 2020 [2]. Cancer has now become the leading cause of death in many countries, accounting for more than a quarter of all deaths. To remove cancer lesions and prolong survival time [3], the mainstay of treatment for many cancers is still systemic chemotherapy [4]. Unfortunately, patients receiving chemotherapy experience multiple co-occurring symptoms [5], which have a negative impact on their functional status, psychosocial dysfunction, and quality of life (QOL) [6]. Compared with non-chemotherapy patients [7], patients receiving chemotherapy experience substantial symptom burden [8].

Multiple symptoms that co-occur and relate to each other form symptom cluster (SC). The science of SC is steadily advancing, and an evaluation of SC is a crucial aspect of symptom management research [9]. SC research represents an important step forward in our understanding of how best to manage the complex symptoms experienced by patients with cancer. As mounting evidence suggests that the presence of SC has a more detrimental effect on treatment outcomes, prognosis, functional status, and QOL than individual symptoms due to their synergistic effects [10], further research is needed to explore the intricate interrelationships among these symptoms and their causal mechanisms in cancer.

There is currently a lack of evidence-based summaries of SC in cancer chemotherapy patients. In a critical work, Ward Sullivan et al. [11] synthesized evidence of SC in cancer patients up to 2016, but this review only included seven studies that accepted cyclophosphamide (CTX) treatment, with the remaining studies including patients receiving various cancer treatments. Given this limitation, it is difficult to determine which SC are associated with specific cancer treatments. A recent systematic review [12] evaluated the advancement of SC research in adult patients undergoing primary or adjuvant chemotherapy, albeit with a restricted scope covering studies from 2017 to 2021, which may have overlooked crucial findings from earlier years. A better understanding of the SC and disease trajectory of this phase can provide valuable insights into the development of personalized treatment plans. Therefore, it is essential to conduct a comprehensive review of the SC of cancer patients undergoing chemotherapy in order to improve the quality of care and outcomes for these patients.

This systematic review therefore aimed to summarize available evidence of evaluating the progress in SC research in adult patients receiving primary or adjuvant chemotherapy in 2001.1~2023.5. Specifically, this paper will: (1) describe the methodological features of SC studies; (2) identify the most salient SC; (3) describe trends in SC over time in cancer patients during chemotherapy.

METHODS

Our reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (Registration No：. INPLASY2024110053).

1. Search strategy

A literature search was conducted between January 2001 and May 2023. Studies were retrieved from PubMed, Ovid MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Web of Science databases. The search strategy used for this review was as follows: (syndrome OR symptom cluster* OR symptom* constellation* OR concurrent symptom* OR multiple symptom* OR symptom* combination* OR co-occurrence symptom*) AND (cancer OR neoplasm OR tumor OR tumors OR Neoplasia* OR Malignant Neoplasm* OR Malignanc* OR Neoplasm*, Malignant OR Benign Neoplasm* OR Neoplasm*, Benign OR Transplant OR leukemia OR lymphoma) AND (chemotherapy OR CTX OR Chemotherapies). A summary of the search strategy was provided in Supplementary Table 1. To avoid omissions, we conducted manual searches of related articles and reference lists.

2. Eligibility criteria

If the following criteria were met, the studies were included: (1) patients diagnosed with cancer and receiving chemotherapy (aged ≥ 18 years); (2) SC extracted during the chemotherapy phase; (3) SC identified by using at least one statistical method; (4) quantitative studies, but not limited to, descriptive research, quasi-experimental, randomized controlled trial (RCT). Studies were excluded if they: (1) involved adolescents and children; (2) cancer patients in the non-chemotherapy period; (3) reviews, meta-analyses, conference abstracts, case reports, qualitative studies, and other non-quantitative study designs; (4) studies pre-defining SC as their outcomes. There are no limitations on the study settings, including but not limited to outpatient settings, and there are no language restrictions.

3. Data extraction

Two reviewers independently screened the titles and abstracts of articles identified from the literature search based on the eligibility criteria. Articles that met the eligibility criteria were then assessed in full text. Conflicts in screening and selection were resolved by a third reviewer. Data from eligible studies were independently extracted by two reviewers, including authors, year of publication, title, country, study design, sample size, patient characteristics, disease type, study setting, statistical methods, symptom assessment tools, extraction timing of SC, summary of SC, symptom dimension(s), key findings and limitations.

4. Assessment of methodological quality

Cross-sectional and longitudinal studies used the Joanna Briggs Institute Critical Appraisal Checklist [13] for Prevalence Studies to evaluate the risk of bias. Each item was recorded as “yes”, “no”, or “cannot determine/not reported/not applicable”. The risk of bias in included RCTs was assessed using the Cochrane risk of bias evaluation tool [14] (Supplementary Table 2). Each item were recorded as “high risk”, “unclear risk”, or “low risk”. Two reviewers independently evaluated the reporting quality. In cases where there were discrepancies in the assessment results, the third reviewer resolved them by a collaborative discussion to obtain a con-sensus (Supplementary Table 3).

RESULTS

1. Search outcome

A total of 2,150 articles were identified through a search of six databases. 1,124 articles were included for initial screening after removing duplicates, of which 990 articles were excluded based on their titles and abstracts. Further review of the full-text articles led to the exclusion of an additional 108 articles. In addition, two studies were added after a manual inspection of references. Consequently, a total of 28 articles [3,5,15-40] met the eligibility criteria for inclusion. The article retrieval process is depicted in Figure 1.

2. Methodological quality of studies

Among the twenty-four descriptive studies, eleven studies did not specify their sampling methods, and the quality evaluation was unclear [15,16,24,26,27,30-32,34,38,40]. Ten studies did not mention the sampling method [16,23,26,27, 30-32,34,38,40], and two studies lacked detailed descriptions of the background and subjects [21,27]. All RCT studies were neutral quality, some sources of bias were lack of random sequence generation, allocation concealment or blinding [25,29,35,36]. Supplementary Table 2 and 3 provides the risk of bias of the included studies.

3. Description of studies

1) Design

Of the included studies, seven were cross-sectional studies [20,22,23,32,33,37,39], seventeen were longitudinal studies [3,5,15-19,21,24,26-28,30,31,34,38,40] and four were a secondary analysis of RCTs [25,29,35,36]. Among the four secondary analysis studies of RCTs, one of the original studies was a cross-sectional study [29] and three were longitudinal studies [25,35,36]. Studies were conducted between 2013 and 2022. Most studies specified that patients recruited from hospitals, comprehensive cancer centers or community-based oncology programs. Only one study included individuals at home [15].

2) Sample characteristics

Among the included studies, eight were conducted in China [3,20,21,23,24,28,38,39], nine in the USA [5,15,16,19,26,29, 30,33,34], three in Korea [27,31,37]. Sweden [25,35] and Thailand [32,40] each had two studies. Indonesia [18], Jordan [36], Sultanate of Oman [22], and the UK [17] were represented by a single study each. Sample sizes ranged from 51 to 1,329. The average age of participants ranged from 35.4 to 64.0 years or was not specified. Most of the study subjects were women, and disease diagnoses included breast, prostate, lung, melanoma, renal, gynecologic, gastrointestinal, gastric, colorectal, bladder cancer, and hematologic malignancy.

3) Symptom assessment tools

There were nineteen studies that utilized the Memorial Symptom Assessment Scale (MSAS) [5,15-20,23,25,26,28, 30-35,38,40], with eight of them being a modified version of the MSAS that included additional symptom [5,15,17,26,30, 33,34,40], and one used the of the Condensed MSAS [23]. Four studies used the MD Anderson Symptom Inventory [3,21,24,39], one studies used the Twenty-Symptom List [27], and one study used the Rotterdam Symptom Checklist [22]. Furthermore, three studies employed multiple symptom assessment tools to measure patients’ symptoms [29,36,37].

4) Analytical technique

Exploratory factor analysis (EFA) was the most used statistical approach in twenty-three studies to derive symptom clusters [3,5,15,16,18-22,24,26,28-34,36-40], followed by principal component analysis (PCA), which was reported in two studies [25,35]. One study utilized a combination of PCA and hierarchical clustering analysis (HCA) [27], while another study used a combination of both EFA and PCA [23]. The remaining study employed other methods, such as the network models of symptoms, the Walktrap algorithm [17].

5) Dimension

In terms of the symptom dimension(s), eight of the studies measured severity [3,15,18,21,24,27,29,31]. Two studies evaluated symptom occurrence [17,20], whereas one study measured symptom distress only [34]. Of the remaining studies, eight studies utilized a comprehensive approach by measuring occurrence, severity, and distress [5,16,19,25,28, 30,35,40]. Six studies measured both occurrence and severity [26,33,36-39], two studies measured occurrence and distress [22,23], and one study measured severity and distress [32].

6) Timing of extraction of symptom clusters

In cross-sectional studies, data were collected during chemotherapy, such as “received at least one chemotherapy treatment”. Most longitudinal studies identified symptom clusters by chemotherapy cycles. The remaining studies of them designated before chemotherapy or at the beginning as the baseline and assessed patients’ symptoms during one week to one month after chemotherapy [16,19,26,29,31,32]. In one secondary analysis of an RCT, symptom clusters were assessed at baseline, 16 weeks and 12 months later [25].

4. Symptom clusters

1) Most common symptom clusters/symptoms

Table 1 shows the most common symptom clusters and their component symptoms in chemotherapy patients. The psychological symptom cluster was the most commonly reported condition across the twenty-five studies, with 2 to 13 symptoms included in the cluster [3,5,16-26,28-35,37-40]. Worrying, feeling nervous, feeling sad, feeling irritable, and distress were common in the cluster. Additionally, sleep-related issues, including difficulty sleeping, and neuro-related symptoms, such as difficulty concentrating, were commonly observed in the psychological symptom cluster. In the three studies that did not feature a psychological symptom cluster, symptoms related to mental health still appeared in other symptom clusters, such as worry and anxiety [15,27,36]. Following the psychological symptom cluster, the gastrointestinal symptom cluster was the second most commonly reported cluster across nineteen studies, with 2 to 16 symptoms included in the cluster [3,5,16,17,19,21,22,24,26-32,35, 36,38,39]. Nausea, lack of appetite, change in the way food tastes, constipation, and dry mouth were identified as the most prevalent symptoms in the gastrointestinal symptom cluster.

2) Evaluation of the stability of symptom clusters across symptom dimensions

According to the research of Harris et al. [41], the term stability is used to describe whether the same symptom cluster can be identified over time or across symptom dimensions, and the term consistency is used to describe whether specific symptoms within a cluster remain the same under the same conditions. There were seventeen studies that evaluated symptom clusters from different dimensions, but only nine studies compared symptom clusters from different dimensions and produced results (Table 2). Four studies found the same symptom clusters in different dimensions, with slightly different composition of symptoms in the cluster [16,22,30,33]. Five studies found that symptom clusters and symptoms within clusters were different in different dimensions [5,19,26,28,32]. Most of the symptom clusters and symptoms within the cluster remained stable, with only a small part varied. However, two studies mentioned the discovery of partial symptom clusters that were stable across dimensions [19,26]. In the remaining eight studies, the purpose of five studies was not related to the stability of symptom clusters [23,25,37,39,40], and three studies did not evaluate the stability of symptom clusters across dimensions [35,36,38].

3) The trend of symptom clusters changing over time

Table 3 shows the trend of symptom clusters changing over time. In total, twenty of the included studies (71.4%) involved an assessment of the changes of the composition of symptom clusters over time. Five studies suggested that symptom clusters remained stable over time, but the composition of symptoms in the cluster was different [3,16,30, 35,40]. Stable symptom clusters included psychological cluster, gastrointestinal cluster, body image cluster, CTX-related symptom cluster, weight change cluster, hormonal cluster and epithelial cluster. The most common symptoms were worrying, feeling sad and constipation. Eleven studies showed that symptom clusters and the symptoms in the cluster were different over time [5,17-19,24,26-28,31,36,38]. Although the most common symptoms were still worrying, feeling sad and constipation, there were also many symptoms such as changes in skin, hair loss, lack of appetite and changes in taste. In addition, in the remaining four longitudinal studies, symptom clusters at only one time point could be extracted [15,21,25,34].

DISCUSSION

This systematic review assessed the advancement of symptom clusters research in adult cancer patients undergoing chemotherapy from 2001 to 2023. We summarized the current methodological characteristics of symptom clusters research, including assessment tools, statistical methods, and other dimensions. The objective of this review is to identify stable symptom clusters and elucidate their characteristics during the course of cancer chemotherapy. This endeavor is aimed at providing evidence that can provide a target for symptom cluster intervention, thereby potentially enhancing the quality of care and overall well-being of cancer patients amid chemotherapy sessions.

Among the twenty-eight studies encompassed in this review, a range of 2~11 symptom clusters were identified. A majority of the studies [5,16-21,24,26,28-34,37,38,40] discerned a higher number of symptom clusters, a likelihood attributed to the extensive array of symptoms and dimensions assessed, which potentially leading to a dispersion of symptom manifestations. Nevertheless, the ideal dimension for appraising symptom clusters remains undetermined. The symptom clusters delineated across varying scales exhibit discrepancies, accentuating the imperative for an exemplary assessment instrument, a comprehensive, multi-dimensional tool, to accurately evaluate symptoms and derive a holistic symptom cluster. Moreover, the absence of a consensus regarding the nomenclature of symptom clusters across studies poses a challenge for comparative analysis of symptom clusters [15-17,19,22-24,27,29,31,32,34,37,40]. The divergence in the identification and naming of symptom clusters underscores the necessity for a standardized approach in symptom cluster research, which can foster a coherent understanding and facilitate comparative analyses. Establishing a consensus on the terminologies and methodologies employed in symptom cluster identification, along with developing a robust, multi-dimensional assessment tool, is paramount to advancing the field. This will not only enable a more precise understanding of symptom cluster dynamics but also pave the way for the development of targeted intervention strategies.

EFA is currently the most widely used statistical method in symptom cluster research. The foundational concept of factor analysis is that observed variables co-vary due to shared underlying causes or latent factors. EFA does not make a priori assumptions about the nature of relationships between the observed variables, allowing a symptom to load onto multiple clusters [41]. Network analysis is an emerging statistical approach [42]. It begins by constructing a symptom network matrix. Community detection algorithms are then employed to identify tightly interconnected symptom clusters [43]. Moreover, in network analysis, various centrality indices are utilized to determine core symptoms, identifying which nodes (i.e., symptoms) might exert the most significant influence on the network. As for which statistical method should be employed for symptom cluster research, there is yet to be a consensus. Some studies have compared EFA, PCA, and HCA to ascertain the consistency of the identified symptom clusters. Results have indicated that the existence and composition of the determined symptom clusters vary depending on the statistical method used.

However, certain symptom clusters or symptoms remain consistently grouped regardless of the analytical approach [44,45]. These symptom clusters, which are still grouped together without the limitation of analytical methods, are common problems faced by patients receiving chemotherapy, which require nurses to raise their priority, set goals to solve the problems, and take appropriate intervention measures. Moreover, establishing standardized protocols and criteria for statistical analysis in symptom cluster research could facilitate more coherent and replicable findings across studies, fostering a deeper, collective understanding of symptom clusters in cancer patients undergoing chemotherapy.

Numerous studies [5,16,19,22,26,28,30,32,33] have compared symptom clusters derived from assessments across different dimensions. The results suggest that while the number and types of symptom clusters remain relatively consistent across these dimensions, the specific symptoms within each cluster can vary. This underscores the variability in how symptoms manifest across different dimensions. This insight prompts healthcare professionals to delve deeper into the multidimensional nature of symptom clusters, fostering a more comprehensive understanding that could significantly enrich the symptom management paradigm in oncological care. By catering to the distinct symptom presentations, healthcare professionals can devise more targeted intervention plans, which could substantially enhance the quality of symptom management, thereby potentially improving the overall quality of life and treatment outcomes for cancer patients.

Psychological and gastrointestinal symptom clusters are the most common among cancer patients during chemotherapy. This suggests that they could potentially be incorporated into standard care procedures for priority or initial intervention. Recognizing these common symptoms early can lead to more effective symptom management, enhancing the quality of life and possibly improving treatment outcomes. On the other hand, hormonal or vasomotor clusters, and other disease-specific symptom groups, require personalized interventions based on the unique characteristics of the cancer [5,16-19,21,24,26,28,29,33]. This tailored approach ensures that the care provided is specific to the individual’s needs, considering both the type of cancer and its progression. The identification of these common symptom clusters paves the way for the development of standardized intervention protocols, which could serve as the cornerstone for initial symptom management strategies in oncological care. Such standardized protocols could significantly expedite the initiation of symptom management interventions, providing a framework for addressing the most common symptom challenges encountered by cancer patients undergoing chemotherapy.

An increasing number of longitudinal studies have focused on the temporal stability of symptom clusters in cancer patients [3,5,16-19,21,24-28,30,31,35,38,40]. Findings suggest that psychological symptom clusters remain relatively consistent over time. This consistent trend may be indicative of the substantial psychological stress and burden that cancer patients often experience. Conversely, other symptom clusters display marked variability, often closely mirroring shifts and changes across different treatment phases. While recognizing common clusters, understanding the dynamic variations of symptom clusters in cancer patients is crucial to adapt to the needs of managing these clusters at different treatment stages.

In the advancing field of symptom science, future research will focus on unraveling the connections between symptom clusters and biomarkers. Characterizing these clusters will deepen our understanding of their underlying mechanisms, paving the way for targeted interventions. Particular emphasis will be on identifying core and primary symptoms to guide clinical prioritization. With a solid understanding of symptom clusters, the implementation of tailored intervention measures will be vital, aiming for a holistic, evidence-based approach to patient care. This approach will not only facilitate more effective symptom management but also potentially lead to improved patient outcomes in the realm of oncological care.

Although this review provides a more comprehensive overview of SC in cancer patients receiving chemotherapy, it has two major limitations. First, there is a high degree of heterogeneity in the methodology used for symptom assessment of patients and symptom cluster identification between the included studies, as well as the naming of symptom clusters. Different methods used to identify symptom clusters will lead to changes in the composition of the identified symptom clusters. Second, this study did not focus specifically on cancer types and stages, and may have overlooked specific symptoms.

CONCLUSION

This review delineates the characteristics of symptom clusters during the chemotherapy phase for cancer patients, examining aspects such as assessment tools, research dimensions, and the number of symptom clusters. In quantitative symptom cluster research, establishing standardized methodologies for the most common or cross-symptom/time-stable symptom clusters is essential to enhance symptom management and ensure precise patient care. Furthermore, the intersection of patient-reported outcomes and biological markers offers a promising avenue for refining symptom cluster interventions. As symptom cluster science matures, a holistic understanding will lead to optimized, patient-centric therapeutic strategies.

Article Information

CONFLICTS OF INTEREST

The authors declared no conflict of interest.

ACKNOWLEDGEMENTS

None.

FUNDING

This study was supported by the Suzhou Science and Technology Development Project Fund in article publishing (No. SKJY2021064). This study was supported by the Science and Technology Project of Suzhou People’s Livelihood Fund in article publishing (No. SYS2020112).

DATA SHARING STATEMENT

Please contact the corresponding author for data availability.

AUTHOR CONTRIBUTIONS

Conceptualization or/and Methodology: Yang P.

Data curation or/and Analysis: Yang P & Mei H & Lu Y.

Funding acquisition: Ge Y & Lu Y.

Investigation: Yang P & Mei H & Zhao H & Wu R & Ge Y & Lu Y.

Project administration or/and Supervision: Ge Y & Lu Y.

Resources or/and Software: Yang P & Ge Y & Lu Y.

Validation: Yang P & Mei H & Zhao H & Wu R & Ge Y & Lu Y.

Visualization: Yang P & Mei H & Zhao H & Wu R & Ge Y & Lu Y.

Writing original draft or/and Review & Editing: Yang P & Mei H & Zhao H & Wu R & Ge Y & Lu Y.

SUPPLEMENTARY DATA

Supplementary data to this article can be found online at https://doi.org/10.15441/jkan.24041.

Supplementary Table 1.

Summary of Search Strategy

jkan-24041-Supplementary-Table-1.pdf

Supplementary Table 2.

Quality Assessment by the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies for Cross-sectional and Longitudinal Studies

jkan-24041-Supplementary-Table-2.pdf

Supplementary Table 3.

Quality Assessment by the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies for Cross-sectional and Longitudinal Studies

jkan-24041-Supplementary-Table-3.pdf

Fig. 1.

Study selection.

Table 1.

Most Common Symptom Clusters/Symptoms

Authors	Symptom assessment tools	The psychological symptom cluster	The gastrointestinal symptom cluster	Other clusters identified
Pozzar et al. [16]	EFA	Yes	Yes	• Hormonal cluster
		- Worrying, hair loss, feeling sad, “I don’t look like myself.”, changes in skin, weight loss, change in the way food tastes, itching, lack of appetite, dizziness, feeling irritable, feeling nervous, abdominal cramps	- Diarrhea, abdominal cramps, constipation, sweats, itching, hot flashes	• Respiratory cluster
				• Weight change cluster
Ma et al. [3]	EFA, Apriori algorithm	Yes	Yes	• Respiratory tract cluster
Ma et al. [3]	EFA, Apriori algorithm	- Fatigue, sadness, distress, drowsiness, pain, numbness	- Nausea, vomiting, constipation, lack of appetite	• Somatic cluster
Kalantari et al. [17]	Network models of symptoms, Walktrap algorithm	Yes	Yes	• Respiratory cluster
		- Difficulty sleeping, worrying, feeling sad, feeling irritable, feeling nervous, difficulty concentrating, lack of energy, feeling drowsy, problems with sexual interest or activity	- Itching, change in the way food tastes, lack of appetite, mouth sores, difficulty swallowing, dry mouth, vomiting, nausea, dizziness, constipation, diarrhea, abdominal cramps, feeling bloated, pain, problems with urination, numbness/tingling in hands/feet	• Weight gain cluster
				• Hormonal cluster
				• Epithelial cluster
				• Sickness behavior cluster
				• Abdominal discomfort cluster
Haryani et al. [18]	EFA	Yes	-	• Pain related cluster
		- “I don’t look like myself.”, feeling sad, worrying, difficulty concentrating, feeling irritable, bloating		• Nutrition cluster
				• Fatigue-treatment cluster
				• Body image cluster
				• Hormonal related cluster
Harris et al. [19]	EFA	Yes	Yes	• Weight gain cluster
		- Worrying, feeling sad, feeling nervous, feeling irritable, difficulty concentrating, “I don’t look like myself.”, problems with sexual interest or activity, difficulty sleeping	- Lack of appetite, weight loss, nausea, change in the way food tastes, vomiting, difficulty swallowing, abdominal cramps, diarrhea, dry mouth, constipation, dizziness	• Respiratory cluster
				• Hormonal cluster
				• Body image cluster
Al Qadire et al. [22]	EFA	Yes	Yes	• Chemotherapy related symptom cluster
Al Qadire et al. [22]	EFA	- Depressed mood, anxiety, feeling tense, worrying, nervousness, irritability, despairing about of future, problems with sexual interest or activity	- Abdominal pain, lack of appetite, nausea, dizziness, diarrhea, acid indigestion/heartburn, constipation	• Fatigue and pain symptom cluster
Fu et al. [20]	EFA	Yes	-	• Fatigue related symptom cluster
		- Feeling sad, worrying, feeling irritable, feeling nervous		• Epithelial symptom cluster
				• Neurologic symptom cluster
				• Malnutrition related symptom cluster
Dan et al. [21]	EFA	Yes	Yes	• Pain related cluster
		- Feeling sad, being distressed, fatigue	- Vomiting, nausea, constipation, lack of appetite	• Cognitive cluster
				• Disease related cluster
				• Treatment related cluster
Li et al. [24]	EFA	Yes	Yes	• Somatic symptom cluster
		- Distress, lack of appetite, sadness, difficulty remembering, difficulty concentrating, difficulty breathing, feeling bloated, feeling irritable, feeling nervous, worrying, weight loss	- Abdominal cramps, constipation, nausea, sweats, lack of appetite, weight loss, changes in skin, “I don’t look like myself.”, change in the way food tastes	• Perceptual symptom cluster
				• Lung cancer-specific symptom cluster
				• Chemotherapy symptom cluster
Chen et al [23]	EFA, PCA	Yes	-	• Nutrition-impairedcluster
		- feeling nervous, Worrying, feeling sad		• Pain-fatigue-sleep cluster
		- feeling nervous, Worrying, feeling sad		• Dry mouth-constipation cluster
Wiggenraad et al. [25]	PCA	Yes	-	• Treatment-related toxicity cluster
Wiggenraad et al. [25]	PCA	- Feeling nervous, lack of appetite, feeling sad, feeling irritable, pain, difficulty sleeping, shortness of breath, “I don’t look like myself.”	-	• Physical cluster
Russell et al. [26]	EFA	Yes	Yes	• Sickness behavior cluster
		- Difficulty concentrating, difficulty breathing, feeling bloated, feeling irritable, feeling nervous, feeling sad, worrying, weight loss	- Abdominal cramps, constipation, nausea, sweats, lack of appetite, weight loss, changes in skin, “I don’t look like myself.”, change in the way food tastes	• Lung cancer-specific cluster
				• Nutritional cluster
				• Epithelial cluster
Rha et al. [27]	HCA, PCA	-	Yes	• Physical-psychological symptom cluster
			- Nausea, lack of appetite, change in the way food tastes	• Fatigue-cognitive symptom cluster
			- Nausea, lack of appetite, change in the way food tastes	• Urosexual symptom cluster
Lin et al. [28]	EFA	Yes	Yes	• Nutritional cluster
		- Feeling nervous, difficulty sleeping, shortness of breath, feeling sad, feeling irritable	- Concentrating, nausea, vomiting, feeling drowsy, “I don’t like myself.”, change in the way food tastes, sweats	• Sickness behavior cluster
				• Neuropathy cluster
				• Body image cluster
Li et al. [29]	EFA	Yes	Yes	• Cognitive cluster
		- Depression, anxiety, fatigue, avoidance of social affairs, change in sleep pattern	- Diarrhea, nausea	• Musculoskeletal cluster
				• Urinary cluster
				• Vasomotor cluster
				• Sexual cluster
				• Weight cluster
Han et al. [30]	EFA	Yes	Yes	• CTX-related cluster
		- Lack of energy, difficulty concentrating, feeling nervous, feeling drowsy, feeling sad, worrying, feeling irritable, changes in skin, problems with sexual interest or activity, “I don’t look like myself.”	- Feeling bloated, abdominal cramps, constipation, nausea, diarrhea	• Weight change cluster
				• Epithelial cluster
Chongkham-ang et al. [32]	EFA	Yes	Yes	• Image and nutrition related cluster
		- Worrying, feeling sad, feeling nervous, feeling irritable, difficulty sleeping, difficulty concentrating, feeling drowsy, sweats	- Nausea, vomiting, difficulty swallowing, feeling bloated, dizziness, lack of energy, shortness of breath, lack of appetite	• Pain and discomfort related cluster
				• Image related cluster
				• Discomfort, nutrition, and elimination related cluster
Sullivan et al. [5]	EFA	Yes	Yes	• Sickness behavior cluster
		- Difficulty concentrating, feeling nervous, feeling sad, worrying, feeling irritable, “I don’t look like myself.”	- Difficulty sleeping, abdominal cramps, shortness of breath, weight loss, feeling bloated, weight gain, nausea, diarrhea	• Hormonal cluster
				• Weight change cluster
				• Epithelial cluster
				• Nutritional cluster
				• CTX-neuropathy cluster
Kim [31]	EFA	Yes	Yes	• Neurocognitive cluster
		- Feeling sad, worrying, lack of energy, feeling irritable, difficulty concentrating	- Dry mouth, change in the way food tastes, difficulty in swallowing, weight loss, nausea	• Body image and decreased vitality cluster
				• Decreased sensory cluster
Wong et al. [33]	EFA	Yes	-	• Sickness behavior cluster
		- Difficulty concentrating, feeling bloated, feeling irritable, feeling nervous, feeling sad, problems with sexual interest or activity, worrying		• Lung cancer-specific cluster
				• Nutritional cluster
				• Epithelial cluster
Cherwin & Perkhounkova [34]	EFA	Yes	-	• Image cluster
		- Emotions cluster: difficulty concentrating, feeling nervous, feeling sad, hair loss, swelling of arms or legs		• Fatigue cluster
				• Bloating cluster
		- Worry cluster: worrying, numbness		• Appetite cluster
Browall et al. [35]	PCA	Yes	Yes	• Physical cluster
Browall et al. [35]	PCA	- Worrying, difficulty concentrating, feeling sad, feeling nervous	- Change in the way food tastes, constipation, diarrhea, lack of appetite, mouth sores, dry mouth	• Physical cluster
Albusoul et al. [36]	EFA	-	Yes	• Treatment-related symptom cluster
Albusoul et al. [36]	EFA	-	- Nausea, appetite, bowel pattern, pain, fatigue	• Treatment-related symptom cluster
Hwang et al. [37]	EFA	Yes	-	• Fatigue-pain cluster
		- Depression, worrying, feeling sad, being sensitive, feeling irritable, dissatisfaction with one's appearance		• Abdominal discomfort cluster
				• Flu-like symptom cluster
				• Fluid accumulation cluster
				• Sexual disturbance cluster
				• Neuropathy cluster
Huang et al. [38]	EFA	Yes	Yes	• Pain-related symptom cluster
		- Feeling nervous, feeling sad, anxiety, feeling irritable	- Lack of appetite, nausea, vomiting, weight loss, change in the way food tastes	• Menopausal symptom cluster
				• Body image symptom cluster
				• Neurologic symptom cluster
Wang & Fu [39]	EFA	Yes	Yes	• Fatigue related cluster
Wang & Fu [39]	EFA	- Being distressed, feeling irritable	- Nausea, vomiting	• Fatigue related cluster
Phligbua et al. [40]	EFA	Yes	-	• Menopausal symptom cluster
		- Feeling sad, worrying, feeling irritable, feeling nervous, pain		• Discomfort symptom cluster
				• Post-operative symptom cluster
				• Gastrointestinal-related fatigue symptom cluster
				• Fatigue symptom cluster
				• Psychologically-related self-image symptom cluster
				• Oral symptom cluster
				• Self-image symptom cluster
				• Disturbed in mood symptom cluster

EFA = Exploratory factor analysis; CTX = Cyclophosphamide; HCA = Hierarchical cluster analysis; PCA = Principal component analysis.

Table 2.

Comparison of Stability of Symptom Clusters across Symptom Dimensions

Authors	Disease types	Symptom cluster	Symptom dimension
Authors	Disease types	Symptom cluster	Occurrence	Severity	Distress
Pozzar et al. [16]	Gynecologic cancer	Psychological cluster	•	•	•
		Gastrointestinal cluster	•	•	•
		Respiratory cluster	•	•	•
		Hormonal cluster	•	•	•
		Weight change cluster	•	•	•
Al Qadire et al. [22]	All types of cancer	Psychological symptom cluster	•	NA	•
		Gastrointestinal symptom cluster	•	NA	•
		Chemotherapy related symptom cluster	•	NA	•
		Fatigue and pain symptom cluster	•	NA	•
Han et al. [30]	Gastrointestinal cancers	Psychological cluster	•	•	•
		GI cluster	•	•	•
		CTX-related cluster	•	•	•
		Weight change cluster	•	•	•
		Epithelial cluster	•	•	•
Wong et al. [33]	Lung cancer	Psychological cluster	•	•	NA
		Sickness behavior cluster	•	•	NA
		Lung cancer-specific cluster	•	•	NA
		Nutritional cluster	•	•	NA
		Epithelial cluster	•	•	NA
Harris et al. [19]	Breast, lung, gastrointestinal or gynaecological cancer	Psychological cluster	•	•	•
		Gastrointestinal cluster	•	•	•
		Weight gain cluster	•	•	•
		Respiratory cluster	•	•	•
		Hormonal cluster	•	•	•
		Body image cluster	•	•
Russell et al. [26]	Lung cancer	Psychological cluster	•	•	NA
		Epithelial/GI cluster	•	•	NA
		Sickness behavior cluster	•	•	NA
		Lung cancer-specific cluster	•	•	NA
		Nutritional cluster	•	•	NA
Lin et al. [28]	Acute myeloid leukemia	Psychological cluster	•	•	•
		GI cluster	•	•	•
		Nutritional cluster	•	•	•
		Sickness behavior cluster	•	•	•
		Neuropathy cluster	•	•	•
		Body image cluster	•	•	•
Chongkham-ang et al. [32]	Breast cancer	Emotion-related cluster	NA	•
		GI and energy related cluster	NA	•
		Image and nutrition related cluster	NA	•
		Pain and discomfort related cluster	NA	•
		Emotion, energy, and pain related cluster	NA		•
		GI related cluster	NA		•
		Image related cluster	NA		•
		Discomfort, nutrition, and elimination related cluster	NA		•
Sullivan et al. [5]	Breast cancer	Psychological cluster	•	•	NA
		GI cluster	•	•	NA
		Sickness behavior cluster	•	•	NA
		Hormonal cluster	•	•	NA
		Weight change cluster	•	•	NA
		Epithelial cluster	•	•	NA
		Nutritional cluster	•	•	NA
		CTX-neuropathy cluster		•	NA

CTX = Cyclophosphamide; GI = Gastrointestinal; NA = Not assessed.

Table 3.

The Trend of Symptom Clusters Changing over Time

Authors	Disease types	Symptom cluster	Time
Authors	Disease types	Symptom cluster	1	2	3	4	5	6
Pozzar et al. [16]	Gynecologic cancer	Psychological cluster	•	•	•	-	-	-
		Gastrointestinal cluster	•	•	•
		Respiratory cluster	•	•	•
		Hormonal cluster	•	•	•
		Weight change cluster	•	•	•
Ma et al. [3]	Lung cancer	Psychological cluster	•		-	-	-	-
		Gastrointestinal cluster	•	•
		Respiratory tract cluster	•	•
		Somatic cluster	•
		Psychological-somatic cluster		•
Kalantari et al. [17]	Breast, gastrointestinal, gynaecological, and lung cancer	Psychological cluster	•	•	•	•	•	•
		Gastrointestinal cluster	•	•	•	•	•	•
		Respiratory cluster	•	•	•	•	•	•
		Weight gain cluster	•	•		•	•	•
		Hormonal cluster	•	•	•	•		•
		Epithelial cluster	•	•		•		•
		Sickness behavior cluster		•	•	•		•
		Abdominal discomfort cluster			•	•	•	•
Haryani et al. [18]	Gynecological cancer	Emotion cluster	•	•	•	•	-	-
		Pain related cluster	•	•		•
		Nutrition cluster	•	•	•	•
		Hormonal related cluster	•
		Fatigue-treatment cluster		•	•
		Body image cluster			•	•
Harris et al. [19]	Breast, lung, gastrointestinal and gynaecological cancer	Psychological cluster	•	•	•	-	-	-
		Gastrointestinal cluster	•	•	•
		Weight gain cluster	•	•	•
		Respiratory cluster	•	•	•
		Hormonal cluster	•
		Body image cluster			•
Li et al. [24]	Lung cancer	Psychological symptom cluster	•	•		-	-	-
		Gastrointestinal symptom cluster		•	•
		Somatic symptom cluster	•
		Perceptual symptom cluster	•	•	•
		Lung cancer-specific symptom cluster	•	•	•
		Chemotherapy symptom cluster		•	•
Russell et al. [26]	Lung cancer	Psychological cluster	•	•	•	-	-	-
		Epithelial/gastrointestinal cluster	•		•
		Sickness behavior cluster	•	•	•
		Lung cancer-specific cluster	•	•	•
		Nutritional cluster	•	•	•
		Epithelial cluster		•
Rha et al. [27]	Breast, stomach, colorectal, lung cancer	Gastrointestinal cluster	•	•	-	-	-	-
		Physical-psychological cluster	•	•
		Fatigue-cognitive cluster	•	•
		Urosexual cluster	•	•
Lin et al. [28]	Acute myeloid leukemia	Psychological cluster		•	•	-	-	-
		Gastrointestinal cluster		•	•
		Nutritional cluster	•		•
		Sickness behavior cluster	•	•
		Neuropathy cluster	•
		Body image cluster	•		•
Han et al. [30]	Gastrointestinal cancers	Psychological cluster	•	•	•	-	-	-
		Gastrointestinal cluster	•
		CTX-related cluster	•	•	•
		Weight change cluster	•	•	•
		Epithelial cluster		•	•
Sullivan et al. [5]	Breast cancer	Psychological cluster	•	•	•	-	-	-
		Gastrointestinal cluster	•	•	•
		Sickness behavior cluster	•
		Hormonal cluster	•	•	•
		Weight change cluster	•
		Epithelial cluster	•	•	•
		Nutritional cluster		•	•
		CTX-neuropathy cluster		•
Kim [31]	Anaplastic astrocytoma, glioblastoma multiforme	Negative emotion cluster	•			-	-	-
		Gastrointestinal cluster		•
		Negative emotion and decreased vitality cluster		•
		Neurocognitive cluster	•
		Body image and decreased vitality cluster			•
		Decreased sensory cluster			•
Browall et al. [35]	Histologically-confirmed stage I to IIIa breast cancer	Emotional cluster	•	•	•	•	-	-
		Gastrointestinal cluster	•	•	•	•
		Physical cluster	•	•	•	•
Albusoul et al. [36]	Breast cancer	Gastrointestinal symptom cluster	•	•			-	-
Albusoul et al. [36]	Breast cancer	Treatment-related symptom cluster	•	•	•	•
Huang et al. [38]	Ovarian cancer	Psychological symptom cluster	•	•	•	•	-	-
		Gastrointestinal symptom cluster		•	•	•
		Pain-related symptom cluster	•	•	•	•
		Menopausal symptom cluster	•	•	•	•
		Body image symptom cluster		•	•	•
		Neurologic symptom cluster			•	•
Phligbua et al. [40]	Stage I~IIIa breast cancer	Psychological symptom cluster	•			-	-	-
		Menopausal symptom cluster	•		•
		Discomfort symptom cluster	•	•	•
		Post-operative symptom cluster	•
		Fatigue symptom cluster	•
		Gastrointestinal-related fatigue symptom cluster		•	•
		Psychologically-related self-image symptom cluster		•
		Oral symptom cluster		•
		Self-image symptom cluster			•
		Disturbed in mood symptom cluster		•	•

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Exploring Symptom Cluster Patterns in Adult Cancer Patients Undergoing Chemotherapy: A Systematic Review

J Korean Acad Nurs. 2024;54(4):478-494. Published online November 25, 2024

DOI: https://doi.org/10.4040/jkan.24041

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Exploring Symptom Cluster Patterns in Adult Cancer Patients Undergoing Chemotherapy: A Systematic Review

Fig. 1. Study selection.

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Exploring Symptom Cluster Patterns in Adult Cancer Patients Undergoing Chemotherapy: A Systematic Review

Authors	Symptom assessment tools	The psychological symptom cluster	The gastrointestinal symptom cluster	Other clusters identified
Pozzar et al. [16]	EFA	Yes	Yes	• Hormonal cluster
		- Worrying, hair loss, feeling sad, “I don’t look like myself.”, changes in skin, weight loss, change in the way food tastes, itching, lack of appetite, dizziness, feeling irritable, feeling nervous, abdominal cramps	- Diarrhea, abdominal cramps, constipation, sweats, itching, hot flashes	• Respiratory cluster
				• Weight change cluster
Ma et al. [3]	EFA, Apriori algorithm	Yes	Yes	• Respiratory tract cluster
Ma et al. [3]	EFA, Apriori algorithm	- Fatigue, sadness, distress, drowsiness, pain, numbness	- Nausea, vomiting, constipation, lack of appetite	• Somatic cluster
Kalantari et al. [17]	Network models of symptoms, Walktrap algorithm	Yes	Yes	• Respiratory cluster
		- Difficulty sleeping, worrying, feeling sad, feeling irritable, feeling nervous, difficulty concentrating, lack of energy, feeling drowsy, problems with sexual interest or activity	- Itching, change in the way food tastes, lack of appetite, mouth sores, difficulty swallowing, dry mouth, vomiting, nausea, dizziness, constipation, diarrhea, abdominal cramps, feeling bloated, pain, problems with urination, numbness/tingling in hands/feet	• Weight gain cluster
				• Hormonal cluster
				• Epithelial cluster
				• Sickness behavior cluster
				• Abdominal discomfort cluster
Haryani et al. [18]	EFA	Yes	-	• Pain related cluster
		- “I don’t look like myself.”, feeling sad, worrying, difficulty concentrating, feeling irritable, bloating		• Nutrition cluster
				• Fatigue-treatment cluster
				• Body image cluster
				• Hormonal related cluster
Harris et al. [19]	EFA	Yes	Yes	• Weight gain cluster
		- Worrying, feeling sad, feeling nervous, feeling irritable, difficulty concentrating, “I don’t look like myself.”, problems with sexual interest or activity, difficulty sleeping	- Lack of appetite, weight loss, nausea, change in the way food tastes, vomiting, difficulty swallowing, abdominal cramps, diarrhea, dry mouth, constipation, dizziness	• Respiratory cluster
				• Hormonal cluster
				• Body image cluster
Al Qadire et al. [22]	EFA	Yes	Yes	• Chemotherapy related symptom cluster
Al Qadire et al. [22]	EFA	- Depressed mood, anxiety, feeling tense, worrying, nervousness, irritability, despairing about of future, problems with sexual interest or activity	- Abdominal pain, lack of appetite, nausea, dizziness, diarrhea, acid indigestion/heartburn, constipation	• Fatigue and pain symptom cluster
Fu et al. [20]	EFA	Yes	-	• Fatigue related symptom cluster
		- Feeling sad, worrying, feeling irritable, feeling nervous		• Epithelial symptom cluster
				• Neurologic symptom cluster
				• Malnutrition related symptom cluster
Dan et al. [21]	EFA	Yes	Yes	• Pain related cluster
		- Feeling sad, being distressed, fatigue	- Vomiting, nausea, constipation, lack of appetite	• Cognitive cluster
				• Disease related cluster
				• Treatment related cluster
Li et al. [24]	EFA	Yes	Yes	• Somatic symptom cluster
		- Distress, lack of appetite, sadness, difficulty remembering, difficulty concentrating, difficulty breathing, feeling bloated, feeling irritable, feeling nervous, worrying, weight loss	- Abdominal cramps, constipation, nausea, sweats, lack of appetite, weight loss, changes in skin, “I don’t look like myself.”, change in the way food tastes	• Perceptual symptom cluster
				• Lung cancer-specific symptom cluster
				• Chemotherapy symptom cluster
Chen et al [23]	EFA, PCA	Yes	-	• Nutrition-impairedcluster
		- feeling nervous, Worrying, feeling sad		• Pain-fatigue-sleep cluster
		- feeling nervous, Worrying, feeling sad		• Dry mouth-constipation cluster
Wiggenraad et al. [25]	PCA	Yes	-	• Treatment-related toxicity cluster
Wiggenraad et al. [25]	PCA	- Feeling nervous, lack of appetite, feeling sad, feeling irritable, pain, difficulty sleeping, shortness of breath, “I don’t look like myself.”	-	• Physical cluster
Russell et al. [26]	EFA	Yes	Yes	• Sickness behavior cluster
		- Difficulty concentrating, difficulty breathing, feeling bloated, feeling irritable, feeling nervous, feeling sad, worrying, weight loss	- Abdominal cramps, constipation, nausea, sweats, lack of appetite, weight loss, changes in skin, “I don’t look like myself.”, change in the way food tastes	• Lung cancer-specific cluster
				• Nutritional cluster
				• Epithelial cluster
Rha et al. [27]	HCA, PCA	-	Yes	• Physical-psychological symptom cluster
			- Nausea, lack of appetite, change in the way food tastes	• Fatigue-cognitive symptom cluster
			- Nausea, lack of appetite, change in the way food tastes	• Urosexual symptom cluster
Lin et al. [28]	EFA	Yes	Yes	• Nutritional cluster
		- Feeling nervous, difficulty sleeping, shortness of breath, feeling sad, feeling irritable	- Concentrating, nausea, vomiting, feeling drowsy, “I don’t like myself.”, change in the way food tastes, sweats	• Sickness behavior cluster
				• Neuropathy cluster
				• Body image cluster
Li et al. [29]	EFA	Yes	Yes	• Cognitive cluster
		- Depression, anxiety, fatigue, avoidance of social affairs, change in sleep pattern	- Diarrhea, nausea	• Musculoskeletal cluster
				• Urinary cluster
				• Vasomotor cluster
				• Sexual cluster
				• Weight cluster
Han et al. [30]	EFA	Yes	Yes	• CTX-related cluster
		- Lack of energy, difficulty concentrating, feeling nervous, feeling drowsy, feeling sad, worrying, feeling irritable, changes in skin, problems with sexual interest or activity, “I don’t look like myself.”	- Feeling bloated, abdominal cramps, constipation, nausea, diarrhea	• Weight change cluster
				• Epithelial cluster
Chongkham-ang et al. [32]	EFA	Yes	Yes	• Image and nutrition related cluster
		- Worrying, feeling sad, feeling nervous, feeling irritable, difficulty sleeping, difficulty concentrating, feeling drowsy, sweats	- Nausea, vomiting, difficulty swallowing, feeling bloated, dizziness, lack of energy, shortness of breath, lack of appetite	• Pain and discomfort related cluster
				• Image related cluster
				• Discomfort, nutrition, and elimination related cluster
Sullivan et al. [5]	EFA	Yes	Yes	• Sickness behavior cluster
		- Difficulty concentrating, feeling nervous, feeling sad, worrying, feeling irritable, “I don’t look like myself.”	- Difficulty sleeping, abdominal cramps, shortness of breath, weight loss, feeling bloated, weight gain, nausea, diarrhea	• Hormonal cluster
				• Weight change cluster
				• Epithelial cluster
				• Nutritional cluster
				• CTX-neuropathy cluster
Kim [31]	EFA	Yes	Yes	• Neurocognitive cluster
		- Feeling sad, worrying, lack of energy, feeling irritable, difficulty concentrating	- Dry mouth, change in the way food tastes, difficulty in swallowing, weight loss, nausea	• Body image and decreased vitality cluster
				• Decreased sensory cluster
Wong et al. [33]	EFA	Yes	-	• Sickness behavior cluster
		- Difficulty concentrating, feeling bloated, feeling irritable, feeling nervous, feeling sad, problems with sexual interest or activity, worrying		• Lung cancer-specific cluster
				• Nutritional cluster
				• Epithelial cluster
Cherwin & Perkhounkova [34]	EFA	Yes	-	• Image cluster
		- Emotions cluster: difficulty concentrating, feeling nervous, feeling sad, hair loss, swelling of arms or legs		• Fatigue cluster
				• Bloating cluster
		- Worry cluster: worrying, numbness		• Appetite cluster
Browall et al. [35]	PCA	Yes	Yes	• Physical cluster
Browall et al. [35]	PCA	- Worrying, difficulty concentrating, feeling sad, feeling nervous	- Change in the way food tastes, constipation, diarrhea, lack of appetite, mouth sores, dry mouth	• Physical cluster
Albusoul et al. [36]	EFA	-	Yes	• Treatment-related symptom cluster
Albusoul et al. [36]	EFA	-	- Nausea, appetite, bowel pattern, pain, fatigue	• Treatment-related symptom cluster
Hwang et al. [37]	EFA	Yes	-	• Fatigue-pain cluster
		- Depression, worrying, feeling sad, being sensitive, feeling irritable, dissatisfaction with one's appearance		• Abdominal discomfort cluster
				• Flu-like symptom cluster
				• Fluid accumulation cluster
				• Sexual disturbance cluster
				• Neuropathy cluster
Huang et al. [38]	EFA	Yes	Yes	• Pain-related symptom cluster
		- Feeling nervous, feeling sad, anxiety, feeling irritable	- Lack of appetite, nausea, vomiting, weight loss, change in the way food tastes	• Menopausal symptom cluster
				• Body image symptom cluster
				• Neurologic symptom cluster
Wang & Fu [39]	EFA	Yes	Yes	• Fatigue related cluster
Wang & Fu [39]	EFA	- Being distressed, feeling irritable	- Nausea, vomiting	• Fatigue related cluster
Phligbua et al. [40]	EFA	Yes	-	• Menopausal symptom cluster
		- Feeling sad, worrying, feeling irritable, feeling nervous, pain		• Discomfort symptom cluster
				• Post-operative symptom cluster
				• Gastrointestinal-related fatigue symptom cluster
				• Fatigue symptom cluster
				• Psychologically-related self-image symptom cluster
				• Oral symptom cluster
				• Self-image symptom cluster
				• Disturbed in mood symptom cluster

Authors	Disease types	Symptom cluster	Symptom dimension
Authors	Disease types	Symptom cluster	Occurrence	Severity	Distress
Pozzar et al. [16]	Gynecologic cancer	Psychological cluster	•	•	•
		Gastrointestinal cluster	•	•	•
		Respiratory cluster	•	•	•
		Hormonal cluster	•	•	•
		Weight change cluster	•	•	•
Al Qadire et al. [22]	All types of cancer	Psychological symptom cluster	•	NA	•
		Gastrointestinal symptom cluster	•	NA	•
		Chemotherapy related symptom cluster	•	NA	•
		Fatigue and pain symptom cluster	•	NA	•
Han et al. [30]	Gastrointestinal cancers	Psychological cluster	•	•	•
		GI cluster	•	•	•
		CTX-related cluster	•	•	•
		Weight change cluster	•	•	•
		Epithelial cluster	•	•	•
Wong et al. [33]	Lung cancer	Psychological cluster	•	•	NA
		Sickness behavior cluster	•	•	NA
		Lung cancer-specific cluster	•	•	NA
		Nutritional cluster	•	•	NA
		Epithelial cluster	•	•	NA
Harris et al. [19]	Breast, lung, gastrointestinal or gynaecological cancer	Psychological cluster	•	•	•
		Gastrointestinal cluster	•	•	•
		Weight gain cluster	•	•	•
		Respiratory cluster	•	•	•
		Hormonal cluster	•	•	•
		Body image cluster	•	•
Russell et al. [26]	Lung cancer	Psychological cluster	•	•	NA
		Epithelial/GI cluster	•	•	NA
		Sickness behavior cluster	•	•	NA
		Lung cancer-specific cluster	•	•	NA
		Nutritional cluster	•	•	NA
Lin et al. [28]	Acute myeloid leukemia	Psychological cluster	•	•	•
		GI cluster	•	•	•
		Nutritional cluster	•	•	•
		Sickness behavior cluster	•	•	•
		Neuropathy cluster	•	•	•
		Body image cluster	•	•	•
Chongkham-ang et al. [32]	Breast cancer	Emotion-related cluster	NA	•
		GI and energy related cluster	NA	•
		Image and nutrition related cluster	NA	•
		Pain and discomfort related cluster	NA	•
		Emotion, energy, and pain related cluster	NA		•
		GI related cluster	NA		•
		Image related cluster	NA		•
		Discomfort, nutrition, and elimination related cluster	NA		•
Sullivan et al. [5]	Breast cancer	Psychological cluster	•	•	NA
		GI cluster	•	•	NA
		Sickness behavior cluster	•	•	NA
		Hormonal cluster	•	•	NA
		Weight change cluster	•	•	NA
		Epithelial cluster	•	•	NA
		Nutritional cluster	•	•	NA
		CTX-neuropathy cluster		•	NA

Authors	Disease types	Symptom cluster	Time
Authors	Disease types	Symptom cluster	1	2	3	4	5	6
Pozzar et al. [16]	Gynecologic cancer	Psychological cluster	•	•	•	-	-	-
		Gastrointestinal cluster	•	•	•
		Respiratory cluster	•	•	•
		Hormonal cluster	•	•	•
		Weight change cluster	•	•	•
Ma et al. [3]	Lung cancer	Psychological cluster	•		-	-	-	-
		Gastrointestinal cluster	•	•
		Respiratory tract cluster	•	•
		Somatic cluster	•
		Psychological-somatic cluster		•
Kalantari et al. [17]	Breast, gastrointestinal, gynaecological, and lung cancer	Psychological cluster	•	•	•	•	•	•
		Gastrointestinal cluster	•	•	•	•	•	•
		Respiratory cluster	•	•	•	•	•	•
		Weight gain cluster	•	•		•	•	•
		Hormonal cluster	•	•	•	•		•
		Epithelial cluster	•	•		•		•
		Sickness behavior cluster		•	•	•		•
		Abdominal discomfort cluster			•	•	•	•
Haryani et al. [18]	Gynecological cancer	Emotion cluster	•	•	•	•	-	-
		Pain related cluster	•	•		•
		Nutrition cluster	•	•	•	•
		Hormonal related cluster	•
		Fatigue-treatment cluster		•	•
		Body image cluster			•	•
Harris et al. [19]	Breast, lung, gastrointestinal and gynaecological cancer	Psychological cluster	•	•	•	-	-	-
		Gastrointestinal cluster	•	•	•
		Weight gain cluster	•	•	•
		Respiratory cluster	•	•	•
		Hormonal cluster	•
		Body image cluster			•
Li et al. [24]	Lung cancer	Psychological symptom cluster	•	•		-	-	-
		Gastrointestinal symptom cluster		•	•
		Somatic symptom cluster	•
		Perceptual symptom cluster	•	•	•
		Lung cancer-specific symptom cluster	•	•	•
		Chemotherapy symptom cluster		•	•
Russell et al. [26]	Lung cancer	Psychological cluster	•	•	•	-	-	-
		Epithelial/gastrointestinal cluster	•		•
		Sickness behavior cluster	•	•	•
		Lung cancer-specific cluster	•	•	•
		Nutritional cluster	•	•	•
		Epithelial cluster		•
Rha et al. [27]	Breast, stomach, colorectal, lung cancer	Gastrointestinal cluster	•	•	-	-	-	-
		Physical-psychological cluster	•	•
		Fatigue-cognitive cluster	•	•
		Urosexual cluster	•	•
Lin et al. [28]	Acute myeloid leukemia	Psychological cluster		•	•	-	-	-
		Gastrointestinal cluster		•	•
		Nutritional cluster	•		•
		Sickness behavior cluster	•	•
		Neuropathy cluster	•
		Body image cluster	•		•
Han et al. [30]	Gastrointestinal cancers	Psychological cluster	•	•	•	-	-	-
		Gastrointestinal cluster	•
		CTX-related cluster	•	•	•
		Weight change cluster	•	•	•
		Epithelial cluster		•	•
Sullivan et al. [5]	Breast cancer	Psychological cluster	•	•	•	-	-	-
		Gastrointestinal cluster	•	•	•
		Sickness behavior cluster	•
		Hormonal cluster	•	•	•
		Weight change cluster	•
		Epithelial cluster	•	•	•
		Nutritional cluster		•	•
		CTX-neuropathy cluster		•
Kim [31]	Anaplastic astrocytoma, glioblastoma multiforme	Negative emotion cluster	•			-	-	-
		Gastrointestinal cluster		•
		Negative emotion and decreased vitality cluster		•
		Neurocognitive cluster	•
		Body image and decreased vitality cluster			•
		Decreased sensory cluster			•
Browall et al. [35]	Histologically-confirmed stage I to IIIa breast cancer	Emotional cluster	•	•	•	•	-	-
		Gastrointestinal cluster	•	•	•	•
		Physical cluster	•	•	•	•
Albusoul et al. [36]	Breast cancer	Gastrointestinal symptom cluster	•	•			-	-
Albusoul et al. [36]	Breast cancer	Treatment-related symptom cluster	•	•	•	•
Huang et al. [38]	Ovarian cancer	Psychological symptom cluster	•	•	•	•	-	-
		Gastrointestinal symptom cluster		•	•	•
		Pain-related symptom cluster	•	•	•	•
		Menopausal symptom cluster	•	•	•	•
		Body image symptom cluster		•	•	•
		Neurologic symptom cluster			•	•
Phligbua et al. [40]	Stage I~IIIa breast cancer	Psychological symptom cluster	•			-	-	-
		Menopausal symptom cluster	•		•
		Discomfort symptom cluster	•	•	•
		Post-operative symptom cluster	•
		Fatigue symptom cluster	•
		Gastrointestinal-related fatigue symptom cluster		•	•
		Psychologically-related self-image symptom cluster		•
		Oral symptom cluster		•
		Self-image symptom cluster			•
		Disturbed in mood symptom cluster		•	•

Table 1. Most Common Symptom Clusters/Symptoms

EFA = Exploratory factor analysis; CTX = Cyclophosphamide; HCA = Hierarchical cluster analysis; PCA = Principal component analysis.

Table 2. Comparison of Stability of Symptom Clusters across Symptom Dimensions