An overview of proceedings, findings, and recommendations from the workshop on "Advancing Symptom Science Through Symptom Cluster Research" sponsored by the National Institute of Nursing Research ...(NINR) and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, is presented. This workshop engaged an expert panel in an evidenced-based discussion regarding the state of the science of symptom clusters in chronic conditions including cancer and other rare diseases. An interdisciplinary working group from the extramural research community representing nursing, medicine, oncology, psychology, and bioinformatics was convened at the National Institutes of Health. Based on expertise, members were divided into teams to address key areas: defining characteristics of symptom clusters, priority symptom clusters and underlying mechanisms, measurement issues, targeted interventions, and new analytic strategies. For each area, the evidence was synthesized, limitations and gaps identified, and recommendations for future research delineated. The majority of findings in each area were from studies of oncology patients. However, increasing evidence suggests that symptom clusters occur in patients with other chronic conditions (eg, pulmonary, cardiac, and end-stage renal disease). Nonetheless, symptom cluster research is extremely limited and scientists are just beginning to understand how to investigate symptom clusters by developing frameworks and new methods and approaches. With a focus on personalized care, an understanding of individual susceptibility to symptoms and whether a "driving" symptom exists that triggers other symptoms in the cluster is needed. Also, research aimed at identifying the mechanisms that underlie symptom clusters is essential to developing targeted interventions.
Symptom assessment is critical to understand the effectiveness of cancer treatment. Traditionally, clinicians have provided the information about cancer patients' symptoms. However, current research ...has shown that there are discrepancies on symptom assessment results reported by patients themselves and clinicians.
The objective of this study was to present an integrative review on studies comparing patient-reported symptoms and clinician-observed symptoms in patients with a diagnosis of cancer.
This was a review of published articles from PubMed, CINAHL, and the Cochrane Database, using the key words symptom or toxicity, and patient-reported, patient-rated, patient-assessed or patient-evaluated, which were combined with cancer, oncology, neoplasm, or tumor.
Clinicians have the propensity to underestimate the incidence, severity, or distress of symptoms experienced by cancer patients. These discrepancies appear to be consistently demonstrated over time and become even more apparent when symptoms are more severe and distressing to patients. In addition, patients report both symptom frequency and severity earlier than clinicians do; patients' symptom assessments are more predictable for daily health status, whereas clinicians' symptom measurements are more related to clinical outcomes.
Healthcare professionals must appreciate that there can be discordance between what they perceive and what patients experience and report. Further research needs to address methodological limitations and weaknesses of existing literature.
Symptoms reported by patients themselves provide the necessary and different insight into cancer and its treatment, compared with those observed by clinicians. The use of patient-reported symptoms should be incorporated into routine clinical practice and not just research studies.
Abstract Purpose To provide an integrative review of the literature on the science of symptom clusters in patients with cancer and establish implications for future studies. Methods Sixty-one ...articles about cancer symptom clusters were selected for review from results of a search in MEDLINE, CINAHL, PsycINFO, Sociological Abstracts and Cochrane databases from 1950 to 2010. Results This review discusses the current research on the definitions, theoretical frameworks, measurements, outcomes, and interventions of symptom clusters in oncology. Although symptom clusters were identified as groups of several related and coexisted symptoms, researchers had different opinion on the least number of and relationships among symptoms in a cluster. Four theoretical frameworks were used, but none of them were specific to guide research in symptom clusters for general cancer population. Most-common symptom approach and all-possible symptom approach had their own characteristics and methods for cluster identification. Functional status and quality of life were major outcomes that were negatively associated with the number or severity of symptom clusters. Interventions with multiple or central symptoms in clusters were two potential ways to improve patients’ symptom experience. Conclusions Despite advances in understanding of symptom clusters, further research is needed to define clusters operationally, and to develop appropriate theoretical frameworks. Methods of cluster identification need further comparison to see which offers the best understanding of symptom clusters. More studies with cross-sectional or longitudinal designs are necessary to explore influences of symptom clusters on patient outcomes, and interventions on symptom clusters.
Purpose
Most survivors of childhood cancer experience subsequent chronic conditions but little is known about concurrent symptoms. This study seeks to identify late effect symptom clusters among ...young pediatric cancer survivors.
Methods
Survivors ≥ 18 or parents of survivors < 18 years enrolled in an institutional cohort study indicated (yes/no) if they experienced certain symptoms after treatment. The sample was randomly divided in half for exploratory factor analyses to identify symptom clusters followed by confirmatory factor analyses. Symptoms with ≥ 10% prevalence were included. Cluster structure generalizability across subgroups was examined using congruence coefficients.
Results
The sample included 579 survivors (74% non-Hispanic white, 45% leukemia, 12.8 ± 4.5 years at survey, 5.9 ± 3.5 years since therapy). Respondents averaged three symptoms. Three clusters were identified: (1) gastrointestinal: abdominal pain, diarrhea, constipation, nausea, vomiting (Cronbach’s
α
= 0.74); (2) psychological: depression, anxiety, memory problems, anger management problems, sleep problems (
α
= 0.71); and (3) neurologic: problems walking, numbness/tingling, fatigue, back pain, chronic pain, weakness/inability to move legs (
α
= 0.71). Confirmatory factor analysis confirmed the three-cluster structure (standardized root mean square residual: 0.09; parsimonious goodness of fit: 0.96; Bentler-Bonett normed fit index: 0.95). The gastrointestinal and psychological clusters were generalizable across most subgroups while the neurologic cluster varied across age and race/ethnicity subgroups.
Conclusion
Three distinct late effect symptom clusters were identified in young childhood cancer survivors with gastrointestinal and psychological clusters remaining relatively stable across subgroups. Future studies should focus on the characteristics of patients who experience these symptoms, especially those with high symptom burden, and the synergistic impact on quality of life.
Purpose
Recent evidence supports a key role of gut microbiome in brain health. We conducted a pilot study to assess associations of gut microbiome with cancer-related fatigue and explore the ...associations with DNA methylation changes.
Methods
Self-reported Multidimensional Fatigue Inventory and stool samples were collected at pre-radiotherapy and one-month post-radiotherapy in patients with head and neck cancer. Gut microbiome data were obtained by sequencing the 16S ribosomal ribonucleic acid gene. DNA methylation changes in the blood were assessed using Illumina Methylation EPIC BeadChip.
Results
We observed significantly different gut microbiota patterns among patients with high vs. low fatigue across time. This pattern was characterized by low relative abundance in short-chain fatty acid–producing taxa (family Ruminococcaceae, genera
Subdoligranulum
and
Faecalibacterium
; all
p
< 0.05), with high abundance in taxa associated with inflammation (genera
Family XIII AD3011
and
Erysipelatoclostridium
; all
p
< 0.05) for high-fatigue group. We identified nine KEGG Orthology pathways significantly different between high- vs. low-fatigue groups over time (all
p
< 0.001), including pathways related to fatty acid synthesis and oxidation, inflammation, and brain function. Gene set enrichment analysis (GSEA) was performed on the top differentially methylated CpG sites that were associated with the taxa and fatigue. All biological processes from the GSEA were related to immune responses and inflammation (FDR < 0.05).
Conclusions
Our results suggest different patterns of the gut microbiota in cancer patients with high vs. low fatigue. Results from functional pathways and DNA methylation analyses indicate that inflammation is likely to be the major driver in the gut-brain axis for cancer-related fatigue.
To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine ...the association between QOL/PS and survival.
Eligible patients were randomized into either an accelerated-fractionation arm or a standard-fractionation arm, and completed the Performance Status Scale for the Head and Neck (PSS-HN), the Head and Neck Radiotherapy Questionnaire (HNRQ), and the Spitzer Quality of Life Index (SQLI) at 8 time points from before treatment to 5 years after treatment.
The results from the analysis of area under the curve showed that QOL/PS was not significantly different between the 2 arms from baseline to year after treatment (P ranged from .39 to .98). The results from general linear mixed models further supported the nonsignificant treatment effects until 5 years after treatment (P=.95, .90, and .84 for PSS-HN Diet, Eating, and Speech, respectively). Before treatment and after 1 year after treatment, p16-positive oropharyngeal cancer (OPC) patients had better QOL than did p16-negative patients (P ranged from .0283 to <.0001 for all questionnaires). However, QOL/PS decreased more significantly from pretreatment to the last 2 weeks of treatment in the p16-positive group than in the p16-negative group (P ranged from .0002 to <.0001). Pretreatment QOL/PS was a significant independent predictor of overall survival, progression-free survival, and local-regional failure but not of distant metastasis (P ranged from .0063 to <.0001).
The results indicated that patients in both arms may have experienced similar QOL/PS. p16-positive patients had better QOL/PS at baseline and after 1 year of follow-up. Patients presenting with better baseline QOL/PS scores had better survival.
Summary Objectives This study is to identify symptom clusters for head and neck (HNC) patients treated with concurrent chemoradiotherapy. Patients and methods A secondary data analysis of 684 HNC ...patients treated on the Radiation Therapy Oncology Group (RTOG) 0129 trial comparing different RT fractionation schedules with concurrent chemotherapy was used to examine clusters. Treatment-related symptoms were measured by clinicians at three time-points during and after chemoradiotherapy using the National Cancer Institute Common Toxicity Criteria v2.0. Exploratory factor analysis was applied to identify symptom clusters, which was further verified by confirmatory factor analysis. Coefficients of congruence and alpha coefficients were employed to examine generalizability of cluster structures over different time-points and in different subgroups. Results Two clusters were identified. The HNC specific cluster is composed of radiodermatitis, dysphagia, radiomucositis, dry mouth, pain, taste disturbance, and fatigue. The gastrointestinal (GI) cluster involves nausea, vomiting, and dehydration. With the exception of patients 65 years old or older, diagnosed with larynx cancer, or with stage III cancer, the two clusters were generalizable to different subgroups defined by age, gender, race, education, marital status, history of tobacco use, treatments, primary sites, disease stages, and tube feedings, as well as to the three symptom assessment time-points. Conclusions The data provides preliminary support for two stable clusters in patients with HNC. These findings may serve to inform the symptom management in clinical practice. Moreover, the findings necessitate future research to examine the generalizability of identified clusters in the late symptom phase or other treatment modalities, and to understand the underlying biological mechanism.
•Fatigue was linked to increased NF-kB and decreased IRF transcriptional activities.•This link was consistent with conserved transcriptional response to adversity (CRTA).•This fatigue-related CRTA ...response was mitigated in patients with HPV-related HNCs.
Previous studies have linked plasma inflammatory markers to elevated fatigue in patients with head and neck cancer (HNC). To identify the molecular mechanisms underlying this association, we conducted promoter-based bioinformatics analyses to determine the relationship between fatigue and specific gene expression profiles associated with inflammation in human papillomavirus (HPV)-related and -unrelated HNC patients undergoing treatment. Patients with newly diagnosed HNC without distant metastasis were assessed at baseline (pre-radiotherapy) and one-month post-radiotherapy. Fatigue was measured by the Multidimensional Fatigue Inventory. Genome-wide gene expression profiles were collected from peripheral blood mononuclear cells (PBMC). Promoter-based bioinformatics analyses were employed to identify transcription control pathways underlying transcriptomic correlates of fatigue in the sample as a whole and in HPV-related and HPV-unrelated HNC patients separately. In transcriptome profiling analyses of PBMC from 44 patients, TELiS bioinformatics analyses linked fatigue to increased nuclear factor-kappa B (NF-kB) transcriptional activity and decreased interferon regulatory factor family (IRF) transcription factor activity. Patients with HPV-related HNC showed lower levels of fatigue-related gene expression profile compared to HPV-unrelated HNC. Fatigue in HNC patients undergoing treatment is associated with gene expression profiles consistent with the conserved transcriptional response to adversity (CTRA) characterized by increased proinflammatory and decreased anti-antiviral transcriptional activity. Interestingly, this CTRA response was mitigated in patients with HPV-related HNC and may explain the lower level of fatigue they experience relative to HPV-unrelated HNC.
Cancer patients experience a cluster of co-occurring psychoneurological symptoms (PNS) related to cancer treatments. The gut microbiome may affect severity of the PNS via neural, immune, and ...endocrine signaling pathways. However, the link between the gut microbiome and PNS has not been well investigated in cancer patients, including those with head and neck cancers (HNCs). This pilot study enrolled 13 patients with HNCs, who reported PNS using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (CTCAEs). Stool specimens were collected to analyze patients' gut microbiome. All data were collected pre- and post-radiation therapy (RT). Associations between the bacterial abundances and the PNS clusters were analyzed using the linear discriminant analysis effect size; functional pathway analyses of 16S rRNA V3-V4 bacterial communities were conducted using Tax4fun. The high PNS cluster had a greater decrease in microbial evenness than the low PNS cluster from pre- to post-RT. The high and low PNS clusters showed significant differences using weighted UniFrac distance. Those individuals with the high PNS cluster were more likely to have higher abundances in phylum
, order
, class
, and four genera (
, and
), while the low PNS cluster had higher abundances in family
and three genera (
, and
). Both glycan metabolism (Lipopolysaccharide biosynthesis) and vitamin metabolism (folate biosynthesis and lipoic acid metabolism) were significantly different between the high and low PNS clusters pre- and post-RT. Our preliminary data suggest that the diversity and abundance of the gut microbiome play a potential role in developing PNS among cancer patients.
Nurses' palliative and hospice care-specific education is associated with the quality of palliative and hospice care that influences health outcomes of patients with life-limiting illnesses and their ...caregivers. However, China lacks measures available to assess nurses' educational needs in palliative and hospice care. The End-of-Life Professional Caregiver Survey (EPCS) is a psychometrically reliable self-reporting scale to measure multidisciplinary professionals' palliative and hospice care educational needs. This study was performed to explore the psychometric properties of the Chinese version of the EPCS (EPCS-C) among Chinese nurses.
We translated and culturally adapted the EPCS into Chinese based on Beaton and colleagues' instrument adaptation process. A cross-sectional study design was used. We recruited 312 nurses from 1482 nurses in a tertiary hospital in central China using convenience sampling to complete the study. Participants completed the EPCS-C and a demographic questionnaire. Exploratory and confirmatory factor analysis was carried out to test and verify the construct validity of the nurse-specific EPCS-C. Cronbach's alpha coefficient was used to appraise the reliability of the nurse-specific EPCS-C.
A three-factor structure of EPCS-C was determined, including cultural, ethical, and national values; patient- and family-centered communication; and effective care delivery. The exploratory factor analysis explained 70.82% of the total variances. The 3-factor solution of the nurse-specific EPCS-C had a satisfactory model fit: χ2 = 537.96, χ2/df = 2.96, CFI = 0.94, RMSEA = 0.079, IFI = 0.94, and GFI = 0.86. Cronbach's alpha coefficient of the overall questionnaire was 0.96.
The nurse-specific EPCS-C showed satisfactory reliability and validity to assess nurses' palliative and hospice care educational need. Further research is required to verify the reliability and validity of the EPCS-C in a larger sample, especially the criterion-related validity.
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