Cancer-Related Symptom Clusters, Eosinophils, and Survival in Hepatobiliary Cancer: An Exploratory Study

Abstract

Context The study of symptom clusters is gaining increased attention in the field of oncology in an attempt to improve the quality of life of patients diagnosed with cancer. Objectives The aims of the present study were to: (1) determine the prevalence and distribution of pain, fatigue, and symptoms of depression and their covariation as a cluster in people with hepatobiliary carcinoma; (2) characterize how variation in each individual symptom and/or their covariation as a cluster are associated with changes in immunity; and (3) determine if the symptom clusters, and associated biomarkers, are related to survival in people diagnosed with hepatobiliary carcinoma. Methods Two hundred and six participants diagnosed with hepatobiliary carcinoma completed a battery of standardized questionnaire measuring cancer-related symptoms. Peripheral blood leukocytes were measured at diagnosis, three- and six-month follow-ups. Survival was measured from the date of diagnosis to death. Results Cancer-related symptoms were prevalent and two-step hierarchical cluster analyses yielded three clusters. High levels of pain, fatigue, and depression were found to be associated with elevated eosinophil percentages (F[1,78]=3.1, P=0.05) at three-month and six-month follow-ups using repeated measures ANOVA. Using multivariate latent growth curve modeling, pain was the primary symptom associated with elevated eosinophil percentages between diagnosis and six months (z=2.24, P=0.05). Using Cox regression, vascular invasion and age were negatively associated with survival (Chi-square=21.6, P=0.03). While stratifying for vascular invasion, Kaplan Meier survival analysis was performed and eosinophil levels above the median for the sample were found to be related to increased survival in patients with and without vascular invasion (Breslow Chi-square=4.9, P=0.03). Symptom clusters did not mediate the relationship between eosinophils and survival. Conclusion Cancer-related symptoms, particularly pain and depression, were associated with increased percentages of eosinophils. The presence of symptoms may reflect tumor cell death and be indicative of response to treatment, or other processes, in patients with hepatobiliary carcinoma.

Advancing Symptom Science Through Symptom Cluster Research: Expert Panel Proceedings and Recommendations

“…In 10 of these papers (2,3,(48)(49)(50)(51)(52)(53)(54)(55), patients with cancer were evaluated. In the 11th paper (56), elderly individuals with impaired cardiac function or heart failure were evaluated.…”

“…The primary mechanisms that were evaluated or discussed included cytokines and inflammation (eight papers: 2,3,49-52,55,56); immune responses (two papers: one on eosinophils [53] and one on viral antibody [48]); activation of the sympathetic nervous system and activation of the hypothalamicpituitary-adrenal (HPA) axis (one paper: 54). Findings on the involvement of each of these four mechanisms in the development of symptom clusters are summarized below.…”

Should we cluster patients or symptoms? The myth of symptom clusters based on ‘depression, insomnia, pain’ and ‘depression, fatigue, pain’

“…Others have measured relationship based on the effect of symptoms on outcomes 3. Most agree that SCs have a greater adverse impact on outcomes than individual symptoms 18 26. In one study (for the preselected symptoms of pain, fatigue and insomnia), regression analysis suggested outcome variance, for example, functional status and correlations between symptoms were tested 3.…”

“…Pain was the only symptom associated with longer survival, perhaps due to more incident pain from greater physical activity in those with better performance status. One study26 did suggest that a proposed DFP cluster was associated with disease progression in hepatobiliary cancer. They found that approximately 25% of patients experienced high levels of depression, fatigue and pain.…”

Clinical and socio-demographic predictors of postoperative vital exhaustion in patients after cardiac surgery

“…49, 50 Relationships between fatigue, depression and elevated eosinophil percentages have been reported in cancer research. 51 Interestingly, increased concentrations of eosinophil-selective chemokine, eotaxin, and eosinophil activation marker, eosinophil cationic protein, were observed in chronic fatigue syndrome and coronary atherosclerosis. 52, 53 This finding highlights a plausible immune-mediated inflammatory mechanism by which exhaustion may promote cardiovascular morbidity and mortality after cardiac surgery.…”