Lower Income, Smoking, Cardiopulmonary Comorbidities, and Higher Symptom Burden Influence the Occurrence of Cough in Patients Receiving Chemotherapy.

OBJECTIVES: To identify subgroups of patients with distinct cough occurrence profiles and evaluate for differences among these subgroups. SAMPLE & SETTING: Outpatients receiving chemotherapy (N = 1,338) completed questionnaires six times over two chemotherapy cycles. METHODS & VARIABLES: Occurrence of cough was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups with distinct cough occurrence profiles. Parametric and nonparametric tests were used to evaluate for differences. RESULTS: Four distinct cough profiles were identified (None, Decreasing, Increasing, and High). Risk factors associated with membership in the High class included lower annual household income; history of smoking; self-reported diagnoses of lung disease, heart disease, and back pain; and having lung cancer. IMPLICATIONS FOR NURSING: Clinicians need to assess all patients with cancer for cough and provide targeted interventions.

Current evidence supporting associations of DNA methylation measurements with survivorship burdens in cancer survivors: A scoping review.

INTRODUCTION: Identifying reliable biomarkers that reflect cancer survivorship symptoms remains a challenge for researchers. DNA methylation (DNAm) measurements reflecting epigenetic changes caused by anti-cancer therapy may provide needed insights. Given lack of consensus describing utilization of DNAm data to predict survivorship issues, a review evaluating the current landscape is warranted. OBJECTIVE: Provide an overview of current studies examining associations of DNAm with survivorship burdens in cancer survivors. METHODS: A literature review was conducted including studies if they focused on cohorts of cancer survivors, utilized peripheral blood cell DNAm data, and evaluated the associations of DNAm and survivorship issues. RESULTS: A total of 22 studies were identified, with majority focused on breast (n = 7) or childhood cancer (n = 9) survivors, and half studies included less than 100 patients (n = 11). Survivorship issues evaluated included those related to neurocognition (n = 5), psychiatric health (n = 3), general wellness (n = 9), chronic conditions (n = 5), and treatment specific toxicities (n = 4). Studies evaluated epigenetic age metrics (n = 10) and DNAm levels at individual CpG sites or regions (n = 12) for their associations with survivorship issues in cancer survivors along with relevant confounding factors. Significant associations of measured DNAm in the peripheral blood samples of cancer survivors and survivorship issues were identified. DISCUSSION/CONCLUSION: Studies utilizing epigenetic age metrics and differential methylation analysis demonstrated significant associations of DNAm measurements with survivorship burdens. Associations were observed encompassing diverse survivorship outcomes and timeframes relative to anti-cancer therapy initiation. These findings underscore the potential of these measurements as useful biomarkers in survivorship care and research.

Multidimensional Model of Energy in Patients With Cancer.

OBJECTIVES: Evidence suggests that energy is a distinct symptom from fatigue in patients with cancer. The purpose of this paper is to present the Multidimensional Model of Energy in Patients with Cancer (MMEPC) that is based on emerging evidence and to make recommendations for clinical practice and future research. METHODS: The literature was reviewed to determine various factors associated with variations in energy in patients with cancer. In addition, some of the emerging evidence in the model is supported by studies of energy in the general population and in patients with other chronic conditions. RESULTS: Based on a review of the literature, specific concepts in the MMEPC include: person factors, clinical factors, cancer-related factors, biological factors, factors associated with energy balance, and co-occurring symptoms. The evidence to support the association between each of these factors and variations in energy levels in patients with cancer is described and synthesized. CONCLUSION: This article provides emerging evidence on factors that influence variations in energy levels in patients with cancer. While the fundamental biobehavioral and biologic mechanisms that underlie variations in energy levels are not well understood, the model can be used to design pre-clinical and clinical studies of energy in patients with cancer. In addition, while emerging evidence supports the hypothesis that fatigue and energy are distinct symptoms, additional research on common and distinct risk factors and underlying mechanisms is warranted to be able to develop and test precision interventions for one or both symptoms. IMPLICATIONS FOR NURSING PRACTICE: The risk factors (eg, being female, sleep quality) associated with variations in energy levels in patients with cancer identified in this paper have important clinical implications. Clinicians can use the identified risk factors to guide their assessments; identify high-risk patients with decrements in energy decrement; and develop targeted energy conservation interventions for the patients.

Neurodegenerative disease pathways are perturbed in patients with cancer who self-report cognitive changes and anxiety: A pathway impact analysis.

BACKGROUND: Cancer-related cognitive impairment (CRCI) and anxiety co-occur in patients with cancer. Little is known about mechanisms for the co-occurrence of these two symptoms. The purposes of this secondary analysis were to evaluate for perturbed pathways associated with the co-occurrence of self-reported CRCI and anxiety in patients with low versus high levels of these two symptoms and to identify potential mechanisms for the co-occurrence of CRCI and anxiety using biological processes common across any perturbed neurodegenerative disease pathways. METHODS: Patients completed the Attentional Function Index and the Spielberger State-Trait Anxiety Inventory six times over two cycles of chemotherapy. Based on findings from a previous latent profile analysis, patients were grouped into none versus both high levels of these symptoms. Gene expression was quantified, and pathway impact analyses were performed. Signaling pathways for evaluation were defined with the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: A total of 451 patients had data available for analysis. Approximately 85.0% of patients were in the none class and 15.0% were in the both high class. Pathway impact analyses identified five perturbed pathways related to neurodegenerative diseases (i.e., amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, prion disease, and pathways of neurodegeneration-multiple diseases). Apoptosis, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress were common biological processes across these pathways. CONCLUSIONS: This study is the first to describe perturbations in neurodegenerative disease pathways associated with CRCI and anxiety in patients receiving chemotherapy. These findings provide new insights into potential targets for the development of mechanistically based interventions.

Stress Exposures Contribute to Worse Joint Morning and Evening Fatigue Profiles in Patients With Cancer During Chemotherapy.

OBJECTIVES: To evaluate differences among stress, resilience, and coping strategies related to morning and evening fatigue profiles (both low, low morning and moderate evening, both moderate, and both high). SAMPLE & SETTING: Data were collected from 1,334 adult patients with cancer receiving chemotherapy. METHODS & VARIABLES: Morning and evening fatigue severity were rated over two cycles of chemotherapy using the Lee Fatigue Scale. Latent profile analysis was used to identify patient subgroups with distinct joint morning and evening profiles. Data were collected on global, cancer-specific, and cumulative life stress; resilience; and coping strategies. Differences among the latent classes were evaluated using parametric and nonparametric tests. RESULTS: Compared to the other three classes, the both high class reported the highest stress scores, highest occurrence of and effects from a variety of stressful life events, lowest resilience scores, and higher use of disengagement coping strategies. The both high class met the criteria for subsyndromal post-traumatic stress disorder. IMPLICATIONS FOR NURSING: When patients report high levels of fatigue, detailed assessments of stress are warranted to provide tailored interventions.

Perturbations in inflammatory pathways are associated with shortness of breath profiles in oncology patients receiving chemotherapy.

PURPOSE: One plausible mechanistic hypothesis is the potential contribution of inflammatory mechanisms to shortness of breath. This study was aimed to evaluate for associations between the occurrence of shortness of breath and perturbations in inflammatory pathways. METHODS: Patients with cancer reported the occurrence of shortness of breath six times over two cycles of chemotherapy. Latent class analysis was used to identify subgroups of patients with distinct shortness of breath occurrence profiles (i.e., none (70.5%), decreasing (8.2%), increasing (7.8%), high (13.5%)). Using an extreme phenotype approach, whole transcriptome differential gene expression and pathway impact analyses were performed to evaluate for perturbed signaling pathways associated with shortness of breath between the none and high classes. Two independent samples (RNA-sequencing (n = 293) and microarray (n = 295) methodologies) were evaluated. Fisher's combined probability method was used to combine these results to obtain a global test of the null hypothesis. In addition, an unweighted knowledge network was created using the specific pathway maps to evaluate for interconnections among these pathways. RESULTS: Twenty-nine Kyoto Encyclopedia of Genes and Genomes inflammatory signaling pathways were perturbed. The mitogen-activated protein kinase signaling pathway node had the highest closeness, betweenness, and degree scores. In addition, five common respiratory disease-related pathways, that may share mechanisms with cancer-related shortness of breath, were perturbed. CONCLUSIONS: Findings provide preliminary support for the hypothesis that inflammation contribute to the occurrence of shortness of breath in patients with cancer. In addition, the mechanisms that underlie shortness of breath in oncology patients may be similar to other respiratory diseases.

Stability and consistency of symptom clusters in younger versus older patients receiving chemotherapy.

BACKGROUND: By 2035, the number of newly diagnosed cancer cases will double and over 50% will be in older adults. Given this rapidly growing demographic, a need exists to understand how age influences oncology patients' symptom burden. The study purposes were to evaluate for differences in the occurrence, severity, and distress of 38 symptoms in younger (< 60 years) versus older (≥ 60 years) oncology patients undergoing chemotherapy and to evaluate for differences in the stability and consistency of symptom clusters across the two age groups. METHODS: A total of 1329 patients were dichotomized into the younger and older groups. Patients completed demographic and clinical questionnaires prior to the initiation of their second or third cycle of chemotherapy. A modified version of Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, and distress of 38 common symptoms associated with cancer and its treatment. Differences between the two age groups in demographic and clinical characteristics and ratings of occurrence, severity, and distress for the 38 symptoms were evaluated using parametric and nonparametric tests. Exploratory factor analyses were done within each age group to identify symptom clusters using symptom occurrence rates. RESULTS: Compared to the younger group (14.8 (± 7.0)), older adults reported a lower mean number of symptoms (12.9 (± 7.2)). Older patients experienced lower occurrence rates for almost 50% of the symptoms. Regarding symptom clusters, an eight-factor solution was selected for both age groups. Across the two age groups, the eight symptom clusters (i.e., physical and cognitive fatigue, respiratory, psychological, hormonal, chemotherapy-related toxicity, weight gain, gastrointestinal, epithelial) were stable. However, symptoms within the physical and cognitive, chemotherapy-related toxicity, and gastrointestinal clusters were not consistent across the age groups. CONCLUSIONS: To be able to provide tailored and effective symptom management interventions to older oncology patients, routine assessments of the core symptoms unique to the symptom clusters identified for this group warrants consideration. The underlying mechanism(s) for these inconsistencies in symptom burden is an important focus for future studies.

Common and distinct risk factors that influence more severe and distressing shortness of breath profiles in oncology outpatients.

BACKGROUND: Shortness of breath occurs in 10%-70% of oncology patients. Very little is known about interindividual variability in its severity and distress and associated risk factors. Using latent profile analyses (LPAs), purpose was to identify subgroups of patients with distinct severity and distress profiles for shortness of breath as single symptom dimensions. In addition, a joint LPA was done using patients' severity AND distress ratings. For each of the three LPAs, differences among the shortness of breath classes in demographic, clinical, symptom, stress, and resilience characteristics were evaluated. METHODS: Patients completed ratings of severity and distress from shortness of breath a total of six times over two cycles of chemotherapy. All of the other measures were completed at enrollment (i.e., prior to the second or third cycle of chemotherapy). Separate LPAs were done using ratings of severity and distress, as well as a joint analysis using severity AND distress ratings. Differences among the latent classes were evaluated using parametric and nonparametric tests. RESULTS: For severity, two classes were identified (Slight to Moderate [91.6%] and Moderate to Severe [8.4%]). For distress, two classes were identified (A Little Bit to Somewhat [83.9%] and Somewhat to Quite a Bit [16.1%]). For the joint LPA, two classes were identified (Lower Severity and Distress [79.9%] and Higher Severity and Distress [20.1%]). While distinct risk factors were associated with each of the LPAs, across the three LPAs, the common risk factors associated with membership in the worse class included: a past or current history of smoking, poorer functional status, and higher comorbidity burden. In addition, these patients had a higher symptom burden and higher levels of cancer-specific stress. CONCLUSIONS: Clinicians can use the information provided in this study to identify high-risk patients and develop individualized interventions.

Distinct Co-occurring Morning and Evening Fatigue Profiles in Patients With Gastrointestinal Cancers Receiving Chemotherapy.

BACKGROUND: Patients with gastrointestinal cancers experience diurnal variations in fatigue severity during chemotherapy that decrease their functional status and quality of life. OBJECTIVES: Study purposes were to identify subgroups of patients with distinct co-occurring morning and evening fatigue profiles and evaluate for differences among these subgroups in demographic, clinical, stress, and symptom characteristics. METHODS: Patients with gastrointestinal cancers (n = 405) completed questionnaires 6 times over 2 cycles of chemotherapy. The Lee Fatigue Scale was used to evaluate diurnal variations in fatigue severity. Latent profile analysis was used to identify subgroups of patients with distinct co-occurring morning AND evening fatigue profiles. Differences among the subgroups in demographic, clinical, stress, and symptom characteristics at enrollment were evaluated using parametric and nonparametric analyses. RESULTS: Two classes were identified, namely: low morning and moderate evening fatigue (ie, Low-Moderate, 60.0%) and high morning and high evening fatigue (ie, Both High, 40.0%). Compared with the Low-Moderate class, the Both High class was significantly younger, female, unmarried, and unemployed and lacked regular exercise. In addition, they had childcare responsibilities, lower annual income, lower functional status, higher comorbidity burden, and self-reported anemia and depression. Patients in the Both High class reported higher levels of anxiety, depressive symptoms, sleep disturbance, pain, and stress, and lower levels of energy and cognitive function. CONCLUSIONS: Findings provide new insights into the risk factors for higher levels of co-occurring morning and evening fatigue in patients with gastrointestinal cancers. IMPLICATIONS FOR PRACTICE: Clinicians can use this information to identify high-risk patients and develop personalized symptom management interventions.