Chemotherapy-associated cognitive impairments in Korean cancer patients: Risk factors and functional outcome.

OBJECTIVE: To identify those experiencing significant self-reported cognitive decline over 2 time points during chemotherapy, examine the risk factors for cognitive decline, and examine differences between those with and without significant decline in functional limitations. METHODS: This secondary analysis used data from 163 cancer patients, collected from a Korean University hospital. Significant decline was determined by 15% or more reduction from baseline in the Functional Assessment of Cancer Therapy-Cognitive Function. Multivariate logistic regression was performed to estimate risk factors. Repeated-measures ANOVA and t tests tested differences in groups with and without cognitive decline in cognitive impairment and functional limitation. RESULTS: About 31% (n = 51) experienced significant cognitive decline. Groups with and without decline significantly differed in cognitive-impairment changes over time (F = 238.49, P < .001) and in functional limitations at follow-up (t test, P < .01). Those experiencing increased fatigue over time (odds = 0.94, P < .05) and those who underwent 2 or more cycles between time 1 and 2 (odds = 2.61; P < .05) had higher risk of significant decline over time during chemotherapy. CONCLUSION: Significant cognitive decline occurred during active chemotherapy; attention to cognitive impairment should be given in the early phase of chemotherapy.

Post-treatment problems of African American breast cancer survivors.

PURPOSE: African American breast cancer survivors (AABCS) have a lower survival rate across all disease stages (79 %) compared with White survivors (92 %) and often have more aggressive forms of breast cancer requiring multimodality treatment, so they could experience a larger burden of post-treatment quality of life (QOL) problems. This paper reports a comprehensive assessment of the number, severity, and domains of problems faced by AABCS within 5 years after treatment completion and identifies subgroups at risk for these problems. METHODS: A population-based random sample was obtained from the Pennsylvania Cancer Registry of African American females over 18 years of age who completed primary treatment for breast cancer in the past 5 years. A mailed survey was used to document survivorship problems. RESULTS: Two hundred ninety-seven AABCS completed the survey. The median number of survivor problems reported was 15. Exploratory factor analysis of the problem scale revealed four domains: emotional problems, physical problems, lack of resources, and sexuality problems. Across problem domains, younger age, more comorbid conditions, and greater medical mistrust were risk factors for more severe problems. CONCLUSIONS: The results demonstrated that AABCS experienced significant problem burden in the early years after diagnosis and treatment. In addition to emotional and physical problem domains that were documented in previous research, two problem domains unique to AABCS included lack of resources and sexuality concerns. At risk groups should be targeted for intervention. The study results reported in this manuscript will inform future research to address problems of AABCS as they make the transition from cancer patient to cancer survivor.

Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update.

BACKGROUND: There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. OBJECTIVES: The objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. METHODS: We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. RESULTS: Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. CONCLUSIONS: Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients' QOL.

Cancer-related fatigue and its impact on functioning.

This article presents the contrasting European and American perspectives on cancer-related fatigue (CRF) and its impact on functioning in cancer survivors. The content is presented in 3 sections: state of the art, intervention studies, and future areas of research, followed by a discussion. Gaps identified include a lack of understanding of the etiology, definition, and measurement of CRF. Models to guide the study of CRF, selection of biomarkers, and design of interventions are needed. There is overlap between Europe and the United States concerning the future directions for research and collaboration related to CRF. The authors suggest the need for international consensus regarding the defining features of CRF in cancer survivors to identify phenotypes, a harmonized measurement of CRF outcomes using instruments that have demonstrated measurement equivalence across languages and cultures, and interventions (including exercise, rehabilitation, and psychoeducational) that have been manualized to permit intervention fidelity across diverse contexts. Coordinated intercontinental efforts would increase understanding of the biological, psychological, and social mechanisms underlying CRF and assist in the design of future intervention studies as well as revisions to clinical guidelines.

Predictors of depression in breast cancer patients treated with radiation: role of prior chemotherapy and nuclear factor kappa B.

BACKGROUND: Depression is common during and after breast cancer treatment. However, the role of specific therapeutic modalities and related biologic mechanisms remains unclear. Radiation is an essential component of breast-conserving therapy and may contribute to depression in patients with breast cancer through the activation of inflammatory pathways. METHODS: Depressive symptoms and inflammatory mediators, including nuclear factor kappa B (NF-κB), were assessed at baseline (before radiation), during radiation, and 6 weeks after radiation in 64 women who had stage 0 through IIIA breast cancer. RESULTS: No significant increases in depressive symptoms occurred during or after radiation, although a number of patients exhibited moderate-to-severe depression throughout the study. Multivariate analyses of baseline factors predictive of depression revealed that educational status, perceived stress, prior chemotherapy, and peripheral blood NF-κB DNA binding all were independent predictors of persistent depressive symptoms after radiation (all P < .05). Of these factors, only prior chemotherapy was associated with inflammatory mediators, including NF-κB DNA binding, soluble tumor necrosis factor-alpha receptor 2, and interleukin-6, which, in univariate analyses predicted depressive symptoms after radiation (all P < .05). Chemotherapy-treated patients also exhibited an over-representation of gene transcripts regulated by NF-κB. CONCLUSIONS: Radiation was not associated with increased depressive symptoms in the current study, but of disease and treatment-related factors, prior chemotherapy predicted significant depression after radiation. Longitudinal studies are warranted to investigate the relationship among prior chemotherapy, inflammation, and persistent depression after breast cancer treatment.

Studying cancer-related fatigue: report of the NCCN scientific research committee.

NCCN convened a committee of experts to make recommendations for future studies of cancer-related fatigue (CRF). The committee reviewed the current data on the incidence, clinical measurement, and treatment of CRF. The assessment of fatigue is largely derived from self-report questionnaires that address the symptom of fatigue, and do not correlate the presence of fatigue with change in physical activity. The committee developed a self-report questionnaire, NCCN Fatigue and Contributing Factors Inventory, which incorporates assessments of fatigue, pain, difficulty sleeping, distress, physical activity, and concurrent medications. A clinical research study using this measure in conjunction with the NCCN Breast Cancer Outcomes Database Project is planned. The committee noted a strong interaction among fatigue, pain, difficulty sleeping, and distress and recommended that future clinical research address these interactions.

Sleep quality after initial chemotherapy for breast cancer.

GOALS OF WORK: The goal of this study is to characterize sleep quality and quantity prior to and in the first three nights after initial chemotherapy for breast cancer. MATERIALS AND METHODS: This study makes use of secondary analysis of data from two separate randomized clinical trials (RCT) of behavioral interventions to improve fatigue and sleep. Patients came from two comprehensive cancer centers, three clinical cancer centers, and 10 community clinics in five states. Participants were women with stage I-IIIA breast cancer treated with anthracycline and/or cyclophosphamide-based regimens. MAIN RESULTS: Baseline data from each RCT were used in the analysis. Sixty-five percent of women self-reported poor sleep in the month preceding chemotherapy using the Pittsburgh Sleep Quality Index (PSQI) score >5. Three nights of actigraphy data indicated a wide range of sleep experience with an average of 10 awakenings and time (minutes) awake after sleep onset (WASO-M) averaging 61 min per night. The first night's sleep was the worst. There was no statistically significant relationship between self-reported poor sleep and sleep measures obtained by actigraphy. Women with poor sleep at baseline (global PSQI >5) had significantly lower (p < 0.001) physical (PCS) and mental (MCS) health status. However, neither the PCS nor MCS was associated with any of the average actigraphy sleep parameters or night 1 parameters in the aggregated sample. Increasing age was also associated with poorer sleep. CONCLUSIONS: A high percent of women with breast cancer begin chemotherapy with disturbed sleep and the initial nights after chemotherapy are characterized by sleep fragmentation that disrupts sleep maintenance. Interventions should focus on strategies to decrease the number and duration of night awakenings. Further research is needed to identify predictors of poor sleep during this time.

I'm so tired: biological and genetic mechanisms of cancer-related fatigue.

OBJECTIVE: The goal of this paper is to discuss cancer-related fatigue (CRF) and address issues related to the investigation into potential biological and genetic causal mechanisms. The objectives are to: (1) describe CRF as a component of quality of life (QOL); (2) address measurement issues that have slowed progress toward an understanding of mechanisms underlying this symptom; (3) review biological pathways and genetic approaches that have promise for the exploration of causal mechanisms of CRF; and (4) offer directions for future research. METHODS: Review, synthesis, and interpretation of the literature. RESULTS: Until recently, CRF and QOL have been understood primarily as subjective patient-reported experiences. With increased understanding of human genetics, theories and research are being expanded to incorporate biological and genetic understandings of these subjective experiences. Proposed biological and genetic mechanisms of CRF that have been examined include cytokine dysregulation, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, five hydroxy tryptophan (5-HT) neurotransmitter dysregulation, circadian rhythm disruption, alterations in adenosine triphosphate (ATP) and muscle metabolism, and vagal afferent activation. Approaches to the study of genetic mechanisms have also been addressed including candidate genes, genome-wide scanning, and gene expression. Based on the review and synthesis of the literature, directions for future research are proposed. CONCLUSIONS: Understanding the biological and genetic basis of CRF has the potential to contribute to a more complete understanding of the genetic determinants of QOL.

Scientific imperatives, clinical implications, and theoretical underpinnings for the investigation of the relationship between genetic variables and patient-reported quality-of-life outcomes.

OBJECTIVES: There is emerging evidence for a genetic basis of patient-reported quality-of-life (QOL) outcomes that can ultimately be incorporated into clinical research and practice. Objectives are (1) to provide arguments for the timeliness of investigating the genetic basis of QOL given the scientific advances in genetics and patient-reported QOL research; (2) to describe the clinical implications of such investigations; (3) to present a theoretical foundation for investigating the genetic underpinnings of QOL; and (4) to describe a series of papers resulting from the GENEQOL Consortium that was established to move this work forward. METHODS: Discussion of scientific advances based on relevant literature. RESULTS: In genetics, technological advances allow for increases in speed and efficiency and decreases in costs in exploring the genetic underpinnings of disease processes, drug metabolism, treatment response, and survival. In patient-based research, advances yield empirically based and stringent approaches to measurement that are scientifically robust. Insights into the genetic basis of QOL will ultimately allow early identification of patients susceptible to QOL deficits and to target care. The Wilson and Cleary model for patient-reported outcomes was refined by incorporating the genetic underpinnings of QOL. CONCLUSIONS: This series of papers provides a path for QOL and genetics researchers to work together to move this field forward and to unravel the intricate interplay of the genetic underpinnings of patient-reported QOL outcomes. The ultimate result will be a greater understanding of the process relating disease, patient, and doctor that will have the potential to lead to improved survival, QOL, and health services delivery.

The establishment of the GENEQOL consortium to investigate the genetic disposition of patient-reported quality-of-life outcomes.

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcomes.

Predictors of the intensity of symptoms in a cluster in patients with breast cancer.

PURPOSE: To examine the influence of selected demographic and clinical variables on the intensity of symptoms in two previously identified symptom clusters (psychoneurological and upper gastrointestinal) across the treatment trajectory for breast cancer. DESIGN: A secondary analysis was conducted with a sample of 282 female breast-cancer patients who were receiving chemotherapy or radiation therapy in two American cancer centers. Data were collected three times across the treatment trajectory: baseline (before chemotherapy or radiation treatment) and two follow-up times after treatment initiation. METHOD: Multiple regression analyses were done at each time point to examine the influence of selected demographic and clinical variables on the intensity of symptoms in each cluster. FINDINGS: Baseline physical performance status was a consistent predictor of symptom intensity in the psychoneurological cluster across time whereas age and treatment modality were consistent predictors of symptom intensity in the upper gastrointestinal cluster. Poor physical performance at baseline predicted more intense psychoneurological symptoms. Younger women and women undergoing chemotherapy experienced more intense gastrointestinal symptoms. In addition, at the second follow-up treatment modality also influenced intensity of symptoms in the psychoneurological cluster and race and baseline physical performance status also influenced the intensity of symptoms in the upper gastrointestinal cluster. CONCLUSIONS: Clinicians can anticipate that younger patients, patients with poor baseline physical performance status, and patients who receive chemotherapy will have more intense treatment-related gastrointestinal and psychoneurological symptoms during adjuvant breast cancer therapy. Further research is needed to determine whether collective management for symptoms in a cluster may be beneficial. CLINICAL RELEVANCE: Clinicians can use findings from the present study to identify patients who need greater attention to symptom assessment and management, including anticipatory counseling of patients and families.

The Brief Perceived Cognitive Impairment Scale-Korean: A Validation Study.

BACKGROUND: Practical brief measures are needed for clinicians and researchers to identify and effectively manage cognitive impairment in cancer patients. OBJECTIVE: This study evaluated the reliability (ie, internal consistency reliability) and validity (ie, construct, convergent, concurrent, and known-group validity) of the Brief Perceived Cognitive Impairment Scale-Korean (BPCIS-K). METHODS: From a university hospital, 249 cancer patients participated. The BPCIS-K was constructed with 6 items evaluating key aspects of cognitive impairment in cancer patients. For internal consistency reliability, Cronbach's α and item-total correlations were evaluated. For construct validity, confirmatory factor analysis was performed. For convergent validity, Pearson correlations were tested with the Functional Assessment of Cancer Therapy-Cognitive Function. For concurrent validity, Pearson correlations were tested with the Functional Assessment of Chronic Illness Therapy-Fatigue. For known-group validity, t tests were performed. RESULTS: The BPCIS-K showed high internal consistency reliability (Cronbach's α = .92; item-total correlations ranged from 0.76 to 0.81). Factor analysis confirmed the scale is unidimensional. It is highly associated with another validated cognitive impairment measure (r = -0.91, P < .001) and moderately correlated with a fatigue measure (r = -0.52, P < .001). In known-group validity, female and patients undergoing treatment experienced more severe impairment than did male patients and patient awaiting treatment (P = .05, P = .08, respectively). CONCLUSION: The BPCIS-K is valid and reliable for assessing cancer patients' perceived cognitive impairment, particularly in concentration, memory, and executive functions. IMPLICATION FOR PRACTICE: This study introduces a practical brief measure to clinicians and researchers.

Evaluation of a Technology-Based Survivor Care Plan for Breast Cancer Survivors: Pre-Post Pilot Study.

BACKGROUND: As of 2016, almost 16 million individuals were cancer survivors, including over 3.5 million survivors of breast cancer. Because cancer survivors are living longer and have unique health care needs, the Institute of Medicine proposed a survivor care plan as a way to alleviate the many medical, emotional, and care coordination problems of survivors. OBJECTIVE: This pilot study for breast cancer survivors was undertaken to: (1) examine self-reported changes in knowledge, confidence, and activation from before receipt to after receipt of a survivor care plan; and (2) describe survivor preferences for, and satisfaction with, a technology-based survivor care plan. METHODS: A single group pretest-posttest design was used to study breast cancer survivors in an academic cancer center and a community cancer center during their medical visit after they completed chemotherapy. The intervention was a technology-based survivor care plan. Measures were taken before, immediately after, and 1 month after receipt of the survivor care plan. RESULTS: A total of 38 breast cancer survivors agreed to participate in the study. Compared to baseline levels before receipt of the survivor care plan, participants reported increased knowledge both immediately after its receipt at the academic center (P<.001) and the community center (P<.001) as well as one month later at the academic center (P=.002) and the community center (P<.001). Participants also reported increased confidence immediately following receipt of the survivor care plan at the academic center (P=.63) and the community center (P=.003) and one month later at both the academic center (P=.63) and the community center (P<.001). Activation was increased from baseline to post-survivor care plan at both the academic center (P=.05) and community center (P<.001) as well as from baseline to 1-month follow-up at the academic center (P=.56) and the community center (P<.001). Overall, community center participants had lower knowledge, confidence, and activation at baseline compared with academic center participants. Overall, 22/38 (58%) participants chose the fully functional electronic survivor care plan. However, 12/23 (52%) in the community center group chose the paper version compared to 4/15 (27%) in the academic center group. Satisfaction with the format (38/38 participants) and the content (37/38 participants) of the survivor care plan was high for both groups. CONCLUSIONS: This study provides evidence that knowledge, confidence, and activation of survivors were associated with implementation of the survivor care plan. This research agrees with previous research showing that cancer survivors found the technology-based survivor care plan to be acceptable. More research is needed to determine the optimal approach to survivor care planning to ensure that all cancer survivors can benefit from it.

Intention to communicate BRCA1/BRCA2 genetic test results to the family.

Guided by the theory of planned behavior, this analysis explores the communication skills of women who had genetic testing for BRCA1 and BRCA2. The key outcome was intention to tell test results to adult first-degree relatives. The theory predicts that global and specific attitudes, global and specific perceived social norms, and perceived control will influence the communication of genetic test results. A logistic regression model revealed that global attitude (p < .05), specific social influence (p < .01), and perceived control (p < .05) were significant predictors of intention to tell. When gender and generation of relatives were added to the regression, participants were more likely to convey genetic test results to female than to male relatives (p < .05) and were also more likely to communicate test results to children (p < .01) or siblings (p < .05) than to parents. However, this association depended on knowing the relative's opinion of genetic testing. Intention to tell was lowest among participants who did not know their relative's opinion. These results extend the theory of planned behavior by showing that gender and generation influence intention when the relative's opinion is unknown.

Management of cancer-related fatigue.

Guidelines for the management of cancer-related fatigue (CRF) emphasize evidence-based strategies for reducing this common symptom in patients with cancer. Exercise has the largest body of data supporting its benefits in reducing CRF. Patient education and counseling also are considered integral to effective CRF management. Additional interventions can be pharmacologic or nonpharmacologic, although a combination of approaches may be employed. Several factors known to be associated with CRF may be particularly amenable to treatment.

Identifying the subtypes of cancer-related fatigue: results from the population-based PROFILES registry.

PURPOSE: Little research has been done to identify possible cancer-related fatigue (CRF) subtypes and to classify cancer survivors accordingly. We aimed to identify CRF subtypes in a large population-based sample of (long term) stage I-III colorectal cancer survivors. We also identified factors associated with the CRF subtypes. METHODS: Respondents completed the Multidimensional Fatigue Inventory and other validated questionnaires on anxiety and reduced positive affect (anhedonia), sleep quality, and lifestyle factors (body mass index and physical activity). Latent class analysis was used to derive the CRF subtypes. Factors associated with the derived CRF subtypes were determined with multinomial logistic regression. RESULTS: Three CRF classes were identified: class 1 (no fatigue and distress, n = 644, 56%), class 2 (low fatigue, moderate distress, n = 256, 22%), and class 3 (high fatigue, moderate distress, n = 256, 22%). Multinomial logistic regression results show that survivors in class 3 were more likely to be female, were treated with radiotherapy, have comorbid diabetes mellitus, and be overweight/obese than survivors in class 1 (reference). Survivors in classes 2 and 3 were also more likely to have comorbid heart condition, report poorer sleep quality, experience anhedonia, and report more anxiety symptoms when compared with survivors in class 1. CONCLUSIONS: Three distinct classes of CRF were identified which could be differentiated with sleep quality, anxiety, anhedonia, and lifestyle factors. IMPLICATIONS FOR CANCER SURVIVORS: The identification of CRF subtypes with distinct characteristics suggests that interventions should be targeted to the CRF subtype.

Phase 2 Study of Weekly Paclitaxel Plus Estramustine in Metastatic Hormone-Refractory Prostate Carcinoma: ECOG-ACRIN Cancer Research Group (E1898) Trial.

INTRODUCTION: This multicenter phase 2 study assessed the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: We enrolled 77 patients who had received no prior chemotherapy for CRPC between 1998 and 2000; a total of 74 subjects were eligible for the study. Each 8-week cycle included paclitaxel 90 mg/m2 provided intravenously weekly for 6 weeks, followed by 2 weeks off therapy and oral estramustine 280 mg twice daily for 3 days beginning 24 hours before the first dose of paclitaxel. The primary end point was rate of objective or prostate-specific antigen (PSA) response at 16 weeks. A 50% response rate was considered of further interest. RESULTS: Eligible patients received a median of 3 cycles (range, 1-10 cycles). The response rate among patients with measurable disease was 34% (95% confidence interval [CI], 19-52). The PSA response rate was 58% (95% CI, 47-70). Clinical benefit rate was 45% (95% CI, 33-57). The median progression-free survival was 5.9 months (95% CI, 4.4-6.7). The median overall survival was 17.6 months (95% CI, 14.6-20.8). The most common clinical grade 3/4 toxicities were fatigue (14%) and sensory neuropathy (7%). Grade 3/4 hematologic toxicities included lymphopenia (21%) and anemia (9%). There was one toxicity-related death. Quality-of-life scores improved by week 8, but the change was not statistically significant. CONCLUSION: The combination has activity defined by PSA declines in CRPC but did not meet the protocol-specified end point for efficacy as defined by objective response rate. Since this study was conducted, more effective, better-tolerated regimens have been developed.

The concept of symptom cluster.

OBJECTIVES: To define the concept of a symptom cluster, evaluate the evidence base in support of it, and address research and clinical implications. DATA SOURCES: Review of descriptive research that examined fatigue, insomnia, pain, or depression in relation to other symptoms. CONCLUSION: More investigation is needed. There is evidence of overlapping variance indicative of a relationship between or among symptoms. Few studies have addressed the outcomes of symptom clusters. There is limited evidence of symptom concurrence or a common biological pathway for clustered symptoms. IMPLICATIONS FOR NURSING PRACTICE: Consideration should be given to assessment and management of fatigue, insomnia, pain, and depression as potential "sentinel symptoms" that could affect patient outcomes.

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

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 cluster research: conceptual, design, measurement, and analysis issues.

Cancer patients may experience multiple concurrent symptoms caused by the cancer, cancer treatment, or their combination. The complex relationships between and among symptoms, as well as the clinical antecedents and consequences, have not been well described. This paper examines the literature on cancer symptom clusters focusing on the conceptualization, design, measurement, and analytic issues. The investigation of symptom clustering is in an early stage of testing empirically whether the characteristics defined in the conceptual definition can be observed in cancer patients. Decisions related to study design include sample selection, the timing of symptom measures, and the characteristics of symptom interventions. For self-report symptom measures, decisions include symptom dimensions to evaluate, methods of scaling symptoms, and the time frame of responses. Analytic decisions may focus on the application of factor analysis, cluster analysis, and path models. Studying the complex symptoms of oncology patients will yield increased understanding of the patterns of association, interaction, and synergy of symptoms that produce specific clinical outcomes. It will also provide a scientific basis and new directions for clinical assessment and intervention.