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J Palliat Med. 2011 Oct;14(10):1149-66. doi: 10.1089/jpm.2010.0507. Epub 2011 Aug 23.

Cancer symptom clusters: clinical and research methodology.

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Taussig Cancer Institute, Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio 44195, USA.



Patients with cancer experience multiple symptoms that frequently appear in groups or clusters. We conducted a comprehensive clinical review of cancer symptom cluster studies to identify common symptom clusters (SC), explore their clinical relevance, and examine their research importance.


Published studies and review articles on cancer SC were obtained through a literature search. We identified 65 reports. These varied in assessment instruments, outcomes, design, population characteristics, and study methods.


Two main approaches to symptom cluster identification were found: clinical and statistical. Clinically determined SC were based upon observations of symptom co-occurrence, associations, or interrelations. These included fatigue-pain, fatigue-insomnia, fatigue-insomnia-pain, depression-fatigue, and depression-pain. They were analyzed by multivariate analysis. They had low to moderate statistical correlations. Disease- or treatment-related SC were influenced by primary cancer site, disease stage, or antitumor treatment. SC determined by statistical analysis were identified by factor and cluster analysis through nonrandom symptom distribution. Nausea-vomiting, anxiety-depression, fatigue-drowsiness, and pain-constipation consistently clustered by either or both of these statistical methods. The individual symptoms of pain, insomnia, and fatigue often appeared in different clusters. A consensus about standard criteria and methodological techniques for cluster analysis should be established.


Several important cancer SC have been identified. Nausea-vomiting, anxiety-depression, and dyspnea-cough clusters were consistently reported. The techniques of symptom cluster identification remain a research tool, but one with considerable potential clinical importance. Further research should validate our analytical techniques, and expand our knowledge about SC and their clinical importance.

[Indexed for MEDLINE]

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