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Should we cluster patients or symptoms? The myth of symptom clusters based on ‘depression, insomnia, pain’ and ‘depression, fatigue, pain’
  1. Aynur Aktas1,2,
  2. Declan Walsh1,2,
  3. Katherine Hauser1,2 and
  4. Lisa Rybicki3
  1. 1Department of Solid Tumor Oncology, Section of Palliative Medicine and Supportive Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA
  2. 2The Harry R. Horvitz Center for Palliative Medicine, Cleveland, Ohio, USA
  3. 3Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
  1. Correspondence to Dr Declan Walsh, Faculty of Health Sciences, Trinity College, Dublin 2, Ireland; walshtd{at}


Context ‘Depression, fatigue, pain’ (DFP) and ‘depression, insomnia, pain’ (DIP) symptom clusters (SCs) have been proposed in cancer. These symptoms are common and co-occur, that is, they constitute clusters of patients rather than symptoms.

Objectives The following research questions were addressed: (1) What is the frequency of co-occurrence of two symptom groups (DFP and DIP) in advanced cancer? (2) What is the degree of symptom item association within each symptom group? (3) Were either of these symptom trios associated with prognosis?

Methods We reanalysed a symptom data set of 1000 patients with advanced cancer. We identified the frequency of co-occurrence of two symptom groups: DFP and DIP, using both prevalence and severity data. The symptom associations were tested by χ2 and Spearman correlations. We also determined whether either of these symptom trios were associated with a major biological outcome, that is, survival by time-to-event analyses.

Results (1) Although DFP and DIP co-occured in about a quarter of the population, they were not SCs, but rather patient clusters. (2) Many persons had only one symptom from any symptom pair, and correlation coefficients were low for all symptom pairs. (3) Neither DFP nor DIP were associated with survival.

Conclusions Neither DFP nor DIP symptom item combinations constituted a specific cancer SC contrary to prior reports. DFP co-occurred in 27% and DIP in only 20%. Additionally, these symptom combinations were not associated with a biological outcome, that is, poor prognosis. Patient subgroups identified by shared symptom experiences alone do not identify SCs.

  • Cancer
  • insomnia
  • Pain
  • symptom clusters

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