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Objectives: To identify subgroups of patients with distinct psychological profiles at the beginning of the COVID-19 pandemic and evaluate for differences., Sample & Setting: Online survey of patients with cancer during the COVID-19 pandemic., Methods & Variables: Patients completed measures of demographic and clinical characteristics, as well as cancer- and COVID-19-related stress, global stress, social isolation, loneliness, financial toxicity, and common symptoms. Latent profile analysis was used to identify distinct psychological profiles., Results: Among 1,145 patients, three subgroups were identified (i.e., no anxiety or depression and normative level of resilience; high depression, high anxiety, and low resilience; and very high depression, very high anxiety, and very low resilience). Patients with the two worst psychological profiles were younger, more likely to be female, more recently diagnosed with cancer, and more likely to have breast cancer., Implications for Nursing: Findings may assist clinicians to identify patients at increased risk for significant psychological morbidity and provide more timely, targeted, and cost-effective interventions.

Background: Interindividual variability in oncology patients' symptom experiences poses significant challenges in prioritizing symptoms for targeted intervention(s). In this study, computational approaches were used to unbiasedly characterize the heterogeneity of the symptom experience of oncology patients to elucidate symptom patterns and drivers of symptom burden., Methods: Severity ratings for 32 symptoms on the Memorial Symptom Assessment Scale from 3088 oncology patients were analyzed. Gaussian Graphical Model symptom networks were constructed for the entire cohort and patient subgroups identified through unsupervised clustering of symptom co-severity patterns. Network characteristics were analyzed and compared using permutation-based statistical tests. Differences in demographic and clinical characteristics between subgroups were assessed using multinomial logistic regression., Results: Network analysis of the entire cohort revealed three symptom clusters: constitutional, gastrointestinal-epithelial, and psychological. Lack of energy was identified as central to the network which suggests that it plays a pivotal role in patients' overall symptom experience. Unsupervised clustering of patients based on shared symptom co-severity patterns identified six patient subgroups with distinct symptom patterns and demographic and clinical characteristics. The centrality of individual symptoms across the subgroup networks differed which suggests that different symptoms need to be prioritized for treatment within each subgroup. Age, treatment status, and performance status were the strongest determinants of subgroup membership., Conclusions: Computational approaches that combine unbiased stratification of patients and in-depth modeling of symptom relationships can capture the heterogeneity in patients' symptom experiences. When validated, the core symptoms for each of the subgroups and the associated clinical determinants may inform precision-based symptom management., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objectives: Evidence suggests that lower levels of morning energy are associated with higher levels of stress and lower levels of resilience in patients receiving chemotherapy. Study purposes were to identify subgroups of patients with distinct morning energy profiles; evaluate for differences among the profiles in demographic and clinical characteristics, as well as measures of stress, resilience, and coping., Methods: A total of 1,343 outpatients receiving chemotherapy completed a demographic questionnaire and measures of global, cancer-related, and cumulative life stress, and resilience at study enrollment. Morning energy was assessed using the Lee Fatigue Scale at six time points over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct morning energy profiles. Differences among the subgroups were evaluated using parametric and nonparametric tests., Results: Three morning energy profiles were identified (i.e., High (17.3%), Low (60.3%), Very Low (22.4%)). Compared to High class, the other two morning energy classes were less likely to be employed; had a lower functional status and a higher comorbidity burden; and were more likely to self-report depression and back pain. For all three types of stress, significant differences were found among the three classes with scores that demonstrated a dose response effect (i.e., High < Low < Very Low; as decrements in morning energy increased, stress scores increased). Compared to High class, Very Low class reported higher rates of physical and sexual abuse. The resilience scores exhibited a dose response effect as well (i.e., High > Low > Very Low). Patients with the two worst energy profiles reported a higher use of disengagement coping strategies., Conclusions: Findings highlight the complex relationships among decrements in morning energy, various types of stress, resilience, and coping in patients undergoing chemotherapy., Implications for Nursing Practice: Clinicians need to assess for stress and adverse childhood experiences to develop individualized management plans to increase patients' energy levels., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2024 American Cancer Society.)

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.

Objectives: To identify subgroups of patients with distinct chemotherapy-induced vomiting (CIV) profiles; determine how these subgroups differ on several demographic, clinical, and symptom characteristics; and evaluate factors associated with chemotherapy-induced nausea and CIV profiles., Sample & Setting: Adult patients (N = 1,338) receiving cancer chemotherapy., Methods & Variables: Data were collected on demographic, clinical, and symptom characteristics. Differences among subgroups of patients with distinct CIV profiles were evaluated using parametric and nonparametric tests., Results: Three CIV profiles (None, Decreasing, and Increasing) were identified. Compared with the None class, Decreasing and Increasing classes were more likely to have lower household income and a higher comorbidity burden, as well as to report higher rates of dry mouth, nausea, diarrhea, depression, anxiety, sleep disturbance, morning fatigue, and pain interference., Implications for Nursing: Clinicians need to assess common and distinct risk factors for CIV and chemotherapy-induced nausea.

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., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate for differences in global, cancer-specific, and cumulative life stress, as well as resilience and use of various coping strategies among five groups (no depression or sleep disturbance, no depression and moderate sleep disturbance, subsyndromal depression and very high sleep disturbance, moderate depression and moderate sleep disturbance [Both Moderate]; and high depression and very high sleep disturbance [Both High])., Sample & Setting: Patients (N = 1,331) receiving chemotherapy were recruited from outpatient oncology clinics., Methods & Variables: Measures of global, cancer-specific, and cumulative life stress, resilience, and coping were obtained. Differences were evaluated using parametric and nonparametric tests., Results: Global and cancer-specific stress scores increased as joint profiles worsened. Both Moderate and Both High classes had cancer-specific stress scores suggestive of post-traumatic stress. Both Moderate and Both High classes reported higher occurrence rates for several stressful life events and higher use of disengagement coping. Both Moderate and Both High classes had resilience scores below the normative score for the United States., Implications for Nursing: Clinicians need to screen vulnerable patients for post-traumatic stress disorder and implement interventions to reduce stress.

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Unrelieved pain and sleep disturbance are common symptoms in oncology patients. Increased stress may be an underlying cause for both symptoms., Objectives: The purposes of this study were to identify subgroups of outpatients with distinct pain and sleep disturbance profiles and to evaluate differences among these subgroups in demographic and clinical characteristics. Differences in global stress, cancer-specific stress, and cumulative life stress, as well as resilience and coping, were evaluated., Methods: Patients (N = 1343) completed self-report questionnaires for demographic and clinical characteristics and stress, resilience, and coping. Latent profile analysis was used to identify subgroups of patients with distinct pain and sleep disturbance profiles. Differences among the subgroups were determined using parametric and nonparametric tests., Results: Three distinct profiles were identified (ie, No Pain + Moderate Sleep Disturbance (SD) (27.6%), Moderate Pain + Moderate SD (38.6%), Severe Pain + High SD (33.8%)). Compared with the other 2 classes, Severe Pain + High SD class was younger, had fewer years of education, was more likely to be female, more likely to live alone, less likely to be employed, and had a higher level of comorbidity. This class had the highest stress scores and was more likely to report higher rates of adverse childhood experiences., Conclusion: Over 70% of our sample reported clinically meaningful levels of both symptoms, and 33.8% reported relatively high rates of adverse childhood experiences., Implication for Practice: Clinicians need to perform routine assessments, particularly of adverse childhood experiences, and initiate appropriate referrals., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., (© 2024. The Author(s).)

Objectives: Purposes were to identify subgroups of adult oncology patients (n = 1342) with distinct joint profiles of worst pain and cognitive function (CF) and evaluate for differences in demographic and clinical characteristics, as well as the severity of three distinct types of stress, resilience, and coping., Data Sources: Measures of pain and CF were evaluated six times over two cycles of chemotherapy. The other measures of demographic and clinical characteristics, stress, resilience, and coping were completed at enrollment (ie, prior to the second or third cycle of chemotherapy)., Results: Using latent profile analysis, four distinct profiles were identified (ie, no pain + moderate CF [27.6%], moderate pain + high CF [22.4%] moderate pain and moderate CF [32.4%, both moderate], severe pain and low CF [17.5%, both severe]). Both moderate and both severe classes reported higher global, cancer-specific, and cumulative life stress, lower levels of resilience, and greater use of disengagement coping strategies. The Both severe class had higher occurrence rates for a number of adverse childhood experiences (ie, family violence in childhood, physical abuse at <16 years, forced sex at <16 years). Risk factors associated with membership in the two worst profiles included: being female, having a lower annual income, having a higher comorbidity burden, and having a poorer functional status., Conclusion: Findings suggest that 72.4% of the patients reported pain scores in the moderate to severe range and 77.6% reported low to moderate levels of CF. Clinicians need to assess for both symptoms and various types of stress on a routine basis., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Various types of stress and the choice of coping strategies may be risk factors for higher levels of sleep disturbance in oncology patients. Purposes were to evaluate for differences in global, cancer-specific, and cumulative life stress, as well as resilience and the use of coping strategies among three subgroups of patients with distinct sleep disturbance profiles (i.e., Low, High, Very High). Oncology outpatients (n = 1331) completed measures of global (Perceived Stress Scale), cancer-specific (Impact of Event Scale-Revised), and cumulative life (Life Stressor Checklist-Revised) stress, resilience (Connor-Davidson Resilience Scale) and coping (Brief Cope) prior to their second or third cycle of chemotherapy. Sleep disturbance was assessed six times over two chemotherapy cycles. Differences were evaluated using parametric and non-parametric tests. All stress measures showed a dose response effect (i.e., as the sleep disturbance profile worsened, levels of all types of stress increased). Compared to Low class, the other two classes reported higher levels of global perceived stress and higher occurrence rates and effect from previous stressful life events. Impact of Event Scale-Revised scores for the Very High class indicated post-traumatic symptomatology. Patients in High and Very High classes had resilience scores below the normative score for the United States population and used a higher number of disengagement coping strategies. Our findings suggest that very high levels of sleep disturbance are associated with higher levels of various types of stress, lower levels of resilience, and higher use of disengagement coping strategies. Clinicians need to perform routine assessments and implement symptom management interventions to reduce stress and encourage the use of engagement coping strategies., (© 2023 John Wiley & Sons Ltd.)

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., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Improved understanding of the stability and consistency of symptom clusters across time, symptom dimensions and cancer diagnoses will lead to refinements in symptom assessments and management, and provide direction for mechanistic studies. Study purposes were to describe the occurrence, severity and distress of 38 symptoms; evaluate the stability and consistency of symptom clusters across a cycle of chemotherapy, three symptom dimensions and four distinct cancer types; and identify common and distinct symptom clusters., Methods: Oncology outpatients (n=1329) completed the Memorial Symptom Assessment Scale prior to their next cycle of chemotherapy (T1), 1 week after chemotherapy (T2) and 2 weeks after chemotherapy (T3). Symptom clusters were identified using exploratory factor analysis using unweighted least squares. GEOMIN rotated factor loadings with absolute values ≥0.40 were considered meaningful. Clusters were stable if they were identified across each time point and/or dimension. Clusters were consistent if the same two or three symptoms with the highest factor loadings were identified across each time point and/or dimension., Results: Patients reported 13.9 (±7.2) symptoms at T1, 14.0 (±7.0) at T2 and 12.2 (±6.8) at T3. Psychological, weight gain, gastrointestinal and respiratory clusters were stable across time and dimensions. Only the psychological, weight gain and respiratory clusters were consistent across time and dimensions., Conclusion: Given the stability of the psychological, weight gain and gastrointestinal clusters across cancer diagnoses, symptoms within these clusters need to be routinely assessed. However, respiratory and hormonal clusters are unique to specific cancer types and the symptoms within these clusters are variable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: In a sample of patients with cancer (n=1145) who were assessed during the height of the COVID-19 pandemic, latent profile analysis was used to identify subgroups of patients with distinct stress profiles and to evaluate for differences in demographic and clinical characteristics and symptom severity scores among these subgroups., Methods: Patients completed measures of cancer-specific and COVID-19 stress, global stress, social isolation, loneliness, depression, state and trait anxiety, morning and evening fatigue, morning and evening energy, sleep disturbance, cognitive function, and pain. Latent profile analysis was used to identify subgroups of patients with distinct stress profiles. Differences among the subgroups in study measures were evaluated using parametric and non-parametric tests., Results: Using clinically meaningful cut-off scores for the stress measures, four distinct stress profiles were identified (ie, none class (51.3%); low stress and moderate loneliness class (24.4%), high stress and moderate loneliness class (14.0%), and very high stress and moderately high loneliness class (high, 10.3%)). Risk factors associated with membership in the high class included: younger age, lower annual household income, lower functional status and higher comorbidity burden. The two worst stress profiles reported clinically meaningful levels of all of the common symptoms associated with cancer and its treatments., Conclusion: Findings from this study, obtained prior to the availability of COVID-19 vaccines and anti-viral medications, provide important 'benchmark data' to evaluate for changes in stress and symptom burden in patients with cancer in the postvaccine era and in patients with long COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Identify subgroups of patients with distinct joint anxiety AND depression profiles and evaluate for differences in demographic and clinical characteristics, as well as stress, resilience, and coping., Design: Longitudinal study., Participants: Patients ( n  = 1328) receiving chemotherapy., Methods: Measures of state anxiety and depression were done six times over two cycles of chemotherapy. All of the other measures were completed prior to second or third cycle of chemotherapy. Latent profile analysis was used to identify the distinct joint anxiety and depression profiles., Findings: Three classes were identified (i.e. Low Anxiety and Low Depression (57.5%); Moderate Anxiety and Moderate Depression (33.7%), High Anxiety and High Depression (8.8%)). For all of the stress measures, a dose response effect was seen among the profiles. Two worst profiles reported higher occurrence rates for a number of adverse childhood experiences., Implications for Providers: Patients need referrals for stress reduction techniques and mental health and social services.

Objectives: Physical and cognitive function are two of the most important patient-reported outcomes. In oncology patients receiving chemotherapy (N = 1331), purposes were to identify subgroups of patients with distinct joint physical and cognitive function profiles and evaluate for differences in demographic and clinical characteristics, severity of common symptoms, and quality of life outcomes., Data Sources: Measures of physical and cognitive functions were obtained six times over two cycles of chemotherapy. All of the other measures were done prior to the second or third cycle of chemotherapy. Latent profile analysis was done to identify the distinct joint physical and cognitive function profiles. Differences among the profiles were evaluated using parametric and nonparametric tests., Conclusion: Five distinct profiles were identified (ie, Very Low Physical and Low Cognitive Function [18.4%; Both Low], Low Physical and High Cognitive Function [19.8%], Moderate Physical and Low Cognitive Function [26.7%], Changing Physical and Cognitive Function [5.4%], and Normal Physical and Cognitive Function [29.7%]). Patients in the Both Low class had the highest symptom burden and the poorest quality of life. Over 70% of the sample had moderate to severe decrements in one or both of these extremely important patient outcomes., Implications for Nursing Practice: Clinicians need to assess for both physical and cognitive function using simple subjective and objective measures., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: We sought to identify subgroups of patients with distinct joint cancer-related cognitive impairment (CRCI) AND anxiety profiles and evaluate for differences in demographic and clinical characteristics, as well as levels of global stress, cancer-specific stress, cumulative life stress, and resilience., Data Sources: Patients (n = 1332) completed the Attentional Function Index and the Spielberger State Anxiety Inventory six times over two cycles of chemotherapy. Global, cancer-specific, and cumulative life stress and resilience were evaluated using Perceived Stress Scale, Impact of Event Scale-Revised, Life Stressor Checklist-Revised, and Connor-Davidson Resilience Scale, respectively. Latent profile analysis was used to identify subgroups of patients with distinct joint CRCI AND anxiety profiles. Differences were evaluated using parametric and nonparametric tests., Results: Three classes were identified (ie, No CRCI and Low Anxiety [57.3%], Moderate CRCI and Moderate Anxiety [34.5%], and High CRCI and High Anxiety [8.2%]). All of the stress measures showed a dose-response effect (ie, as the CRCI AND anxiety profile worsened, scores for all three types of stress increased). The two highest symptom classes reported higher occurrence rates for six specific stressors (eg, emotional abuse, physical abuse, sexual harassment)., Conclusions: Findings suggest that higher levels of co-occurring CRCI AND anxiety are associated with some common risk factors, as well as higher levels of stress and lower levels of resilience. Increased knowledge of modifiable risk factors and sources of stress associated with the co-occurrence of these two symptoms will assist clinicians to identify high-risk patients and implement individualized interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Evaluate for perturbed signaling pathways associated with subgroups of patients with low versus high levels of state anxiety. These pathways were compared to the pathways identified across eight network pharmacology studies of the anxiolytic effect(s) of a variety of compounds., Methods: Adult outpatients had a diagnosis of breast, gastrointestinal, gynecological, or lung cancer; had received chemotherapy within the preceding four weeks; and were scheduled to receive at least two additional cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct anxiety profiles based on Spielberger State Anxiety Inventory scores that were obtained six times over two cycles of chemotherapy. Blood samples were processed using RNA sequencing (i.e., RNA-seq sample, n = 244) and microarray (i.e., microarray sample; n = 256) technologies. Pathway perturbations were assessed using pathway impact analysis. Fisher's combined probability method was used to combine test results using a false discovery rate of 0.01., Results: In the RNA-seq sample, 62.3% and 37.7% of the patients were in the low- and high-anxiety classes, respectively. In the microarray sample, 61.3% and 38.7% were in the low and high-anxiety classes, respectively. Forty-one perturbed signaling pathways were identified. Eight of these pathways were common to those identified in the network pharmacology studies., Conclusions: Findings increase our knowledge of the molecular mechanisms that underlie anxiety in patients receiving chemotherapy. This study provides initial insights into how anxiety in patients with cancer may share common mechanisms with anxiety in patients with other clinical conditions., (© 2023. The Author(s).)

Objectives: Among four classes of patients with distinct shortness of breath profiles, evaluate for differences in levels of global, cancer-specific, and cumulative life stress, as well as resilience; evaluate for differences in the occurrence rates for various stressful life events, and evaluate for differences in the severity of common co-occurring symptoms., Data Sources: Outpatients (N = 1338) completed questionnaires six times over two cycles of chemotherapy. The occurrence of shortness of breath was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups of patients with distinct shortness of breath profiles. Differences among the classes were evaluated using parametric and nonparametric tests., Conclusion: Shortness of breath classes were labeled based on their distinct occurrence trajectories: None (70.5%), Decreasing (8.2%), Increasing (7.8%), and High (13.5%). Compared to None class, Decreasing and High classes had higher global and cancer-specific stress scores. The High class reported higher occurrence rates for several adverse childhood experiences. Compared to None class, Decreasing and High classes had higher depression, anxiety, and morning fatigue scores and lower morning energy and cognitive function scores., Implications for Nursing Practice: Given the additive or synergistic relationships between stress, co-occurring symptoms, and shortness of breath, multimodal interventions that include stress management, exercise training, and/or symptom management may decrease shortness of breath in oncology patients., Competing Interests: Declaration of Competing Interest Dr. Wong reported conflicts of interest outside of the submitted work: An immediate family member is an employee of Genentech with stock ownership and Dr. Wong receives royalties from UpToDate. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Little is known about hearing loss and tinnitus associated with neurotoxic chemotherapy. Study evaluated for differences in occurrence rates and effects of hearing loss and tinnitus in survivors who received a platinum alone, a taxane alone or a platinum and taxane containing regimen., Methods: Total of 273 survivors with breast, gastrointestinal, gynaecological or lung cancer completed self-report measures of hearing loss and tinnitus and had an audiometric assessment that obtained pure tone air conduction thresholds bilaterally at frequencies of between 0.25 kHz to 16.0 kHz. To adjust for age-related and gender-related changes in hearing, each survivor's audiogram was evaluated using the National Health and Nutrition Examination Survey-modified Occupational Safety and Health Administration standards. Survivor was classified as having hearing loss if at any frequency they scored poorer than the 50th percentile for their age and gender. Survivors were categorised as having tinnitus if they reported that for > 10% of their time awake, they were consciously aware of their tinnitus. Differences among the chemotherapy groups were evaluated using parametric and non-parametric tests., Results: For most of the demographic and clinical characteristics, no differences were found among the three chemotherapy groups. Occurrence rates for audiogram-confirmed hearing loss ranged from 52.3% to 71.4%. Occurrence rates for tinnitus ranged from 37.1% to 40.0%. No differences were found among the three chemotherapy groups in the occurrence rates or effects of hearing loss and tinnitus., Conclusion: These findings suggest that regardless of the chemotherapy regimen common mechanistic pathway(s) may underlie these two neurotoxicities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate for subgroups of patients with distinct symptom profiles and differences in demographic and clinical characteristics and stress and resilience among these subgroups., Sample & Setting: 1,145 patients with cancer aged 18 years or older completed a survey online. Data were collected between May 2020 and February 2021., Methods & Variables: Patients completed measures for depression, state anxiety, cognitive function, morning fatigue, evening fatigue, morning energy, evening energy, sleep disturbance, pain, stress, and resilience. Latent class profile analysis was used to identify subgroups of patients with distinct symptom profiles. Differences among the subgroups on study measures were evaluated using parametric and nonparametric tests., Results: Four distinct profiles were identified (none, low, high, and very high). Patients in the high and very high classes reported clinically meaningful levels of all nine symptoms. Differences among the four profiles for stress and resilience exhibited a dose-response effect., Implications for Nursing: Findings can serve as benchmark data of the symptom burden of patients with cancer following the COVID-19 pandemic.

Background: Evaluate for differences in occurrence, severity, and distress ratings for 32 symptoms between younger older adults (YOA, < 70 years) and older adults (OA, ≥ 70 years) at initiation of chemotherapy., Methods: Patients (n = 125) were recruited prior to the initiation of chemotherapy and completed the Memorial Symptom Assessment Scale. Differences in occurrence, severity, and distress ratings were evaluated using Independent sample t-tests and Chi-square or Fisher's exact tests., Results: On average, the older patients reported ten concurrent symptoms that equates with a moderate symptom burden. Symptoms with the highest occurrence rates were not always the most severe and/or the most distressing. Few age-related differences were found in patients' symptom experiences. When age-related differences were identified, OA reported lower occurrence, severity, and distress ratings. Nine of the ten symptoms with highest occurrence rates were common for both age groups. For severity and distress, only half of the symptoms were common. In terms of severity and distress, all of the top ten ranked symptoms were in the moderate to severe range., Conclusions: Both YOA and OA reported a moderate symptom burden and severity and distress scores in the moderate to severe range. The symptoms with the highest occurrence rates were not always the most severe/or the most distressing. Our findings suggest that different dimensions of the symptom experience (i.e., occurrence, severity, and distress) warrant evaluation in older oncology patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: In a sample of patients with gynecologic cancers who are receiving chemotherapy, subgroups of patients with distinct state anxiety profiles were identified, and differences among the subgroups in demographic and clinical characteristics, stress, exposure to stressful life events, resilience, and coping behaviors were evaluated., Data Sources: Patients (n = 230) completed questionnaires six times over two chemotherapy cycles. State anxiety was measured using the Spielberger State Anxiety Inventory. Subgroups of patients with distinct state anxiety profiles were identified using latent profile analysis. Differences among the classes were assessed using parametric and nonparametric tests., Conclusion: Three distinct state anxiety profiles were identified: low (55.2%), moderate (38.3%), and very high (6.5%). Compared with the low class, persons in the other two classes had lower functional status, more comorbidities, higher perceived stress, and lower resilience and were more likely to report a history of depression and to use disengagement coping strategies. Compared with the low class, the very high class was more likely to report childcare responsibilities; have a history of lung disease, stomach disease, or low back pain; have experienced physical neglect, serious money problems, a serious disaster, or foster care; or were a caregiver for someone with a severe disability., Implications for Nursing Practice: Nearly 45% of patients reported clinically meaningful levels of state anxiety that persisted over two cycles of chemotherapy. Experiences with a variety of stressors may be risk factors for higher levels of anxiety during chemotherapy. Clinicians need to perform comprehensive social histories and assess for anxiety in patients receiving chemotherapy., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: Pain is common and variable in its severity among hospitalized patients with cancer. Although biopsychosocial factors are well established as modulators of chronic pain, less is known about what patient-level factors are associated with worse pain outcomes among hospitalized cancer patients. This prospective cohort study included patients with active cancer presenting to the emergency department (ED) with pain severity of ≥4/10 and followed pain outcomes longitudinally throughout hospital admission. Baseline demographic, clinical, and psychological factors were assessed on ED presentation, and daily average clinical pain ratings and opioid consumption during hospitalization were abstracted. Univariable and multivariable generalized estimating equation analyses examined associations of candidate biopsychosocial, demographic, and clinical predictors with average daily pain and opioid administration. Among 113 hospitalized patients, 73% reported pain as the primary reason for presenting to the ED, 43% took outpatient opioids, and 27% had chronic pain that predated their cancer. Higher pain catastrophizing ( B = 0.1, P ≤ 0.001), more recent surgery ( B = -0.2, P ≤ 0.05), outpatient opioid use ( B = 1.4, P ≤ 0.001), and history of chronic pain before cancer diagnosis ( B = 0.8, P ≤ 0.05) were independently associated with greater average daily pain while admitted to the hospital. Higher pain catastrophizing ( B = 1.6, P ≤ 0.05), higher anxiety ( B = 3.7, P ≤ 0.05), lower depression ( B = -4.9, P ≤ 0.05), metastatic disease ( B = 16.2, P ≤ 0.05), and outpatient opioid use ( B = 32.8, P ≤ 0.001) were independently associated with higher daily opioid administration. Greater psychological distress, especially pain catastrophizing, as well as pain and opioid use history, predicted greater difficulty with pain management among hospitalized cancer patients, suggesting that early assessment of patient-level characteristics may help direct consultation for more intensive pharmacologic and nonpharmacologic interventions., (Copyright © 2023 International Association for the Study of Pain.)

Objective/background: An emerging area of research is the relationship between sleep disturbance and decrements in energy. Given the paucity of research on the co-occurrence of these two symptoms, study purposes were to identify subgroups of oncology patients with distinct joint sleep disturbance AND morning energy profiles and evaluate for differences among the subgroups in demographic, clinical, and sleep disturbance characteristics, as well as the severity of other common symptoms and QOL outcomes., Patients/methods: Patients (n = 1336) completed measures of sleep disturbance and energy 6 times over two cycles of chemotherapy. All of the other measures were completed at enrollment. Latent profile analysis was used to identify the distinct joint sleep disturbance and morning energy profiles., Results: Three distinct profiles were identified (i.e., Low Sleep Disturbance and High Morning Energy (Normal, 20.6%), Moderate Sleep Disturbance and Low Morning Energy (Moderately Severe, 52.1%), Very High Sleep Disturbance and Very Low Morning Energy (Very Severe, 27.3%). Compared to Normal class, other two classes were more likely to be female, less likely to be employed, and had higher comorbidity burden and poorer functional status. Symptom scores and QOL outcomes exhibited a dose response effect (i.e., as the profile worsened, symptom scores increased and QOL scores decreased)., Conclusions: Given the associations between sleep disturbance and decrements in energy and a higher symptom burden, poorer QOL outcomes, and increased mortality, assessment of these two symptoms needs to be a high priority for clinicians and appropriate interventions initiated., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Up to 45% of patients report cancer-related cognitive impairment (CRCI). A variety of characteristics are associated with the occurrence and/or severity of CRCI. However, an important gap in knowledge of risk factors for CRCI is the relative contribution of each factor. The multifactorial model of cancer-related cognitive impairment (MMCRCI) is a conceptual model of CRCI that can be used to evaluate the strength of relationships between various factors and CRCI., Objectives: The purpose of this study was to use structural regression methods to evaluate the MMCRCI using data from a large sample of outpatients receiving chemotherapy ( n = 1,343). Specifically, the relationships between self-reported CRCI and four MMCRCI concepts (i.e., social determinants of health, patient-specific factors, treatment factors, and co-occurring symptoms) were examined. The goals were to determine how well the four concepts predicted CRCI and determine the relative contribution of each concept to deficits in perceived cognitive function., Methods: This study is part of a larger, longitudinal study that evaluated the symptom experience of oncology outpatients receiving chemotherapy. Adult patients were diagnosed with breast, gastrointestinal, gynecological, or lung cancer; had received chemotherapy within the preceding 4 weeks; were scheduled to receive at least two additional cycles of chemotherapy; were able to read, write, and understand English; and gave written informed consent. Self-reported CRCI was assessed using the attentional function index. Available study data were used to define the latent variables., Results: On average, patients were 57 years of age, college educated, and with a mean Karnofsky Performance Status score of 80. Of the four concepts evaluated, whereas co-occurring symptoms explained the largest amount of variance in CRCI, treatment factors explained the smallest amount of variance. A simultaneous structural regression model that estimated the joint effect of the four exogenous latent variables on the CRCI latent variable was not significant., Discussion: These findings suggest that testing individual components of the MMCRCI may provide useful information on the relationships among various risk factors, as well as refinements of the model. In terms of risk factors for CRCI, co-occurring symptoms may be more significant than treatment factors, patient-specific factors, and/or social determinants of health in patients receiving chemotherapy., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Morning and evening fatigue are distinct and distressing symptoms experienced during chemotherapy that demonstrate a large amount of interindividual variability., Objectives: The objectives of this study were to identify subgroups of patients with distinct morning and evening fatigue co-occurrence profiles and evaluate for differences among these subgroups in demographic, clinical, and symptom characteristics and quality of life., Methods: Oncology patients ( n = 1,334) completed the Lee Fatigue Scale to self-report morning and evening fatigue, six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct morning and evening physical fatigue profiles., Results: Four distinct morning and evening fatigue profiles were identified (i.e., Both Low, Low Morning + Moderate Evening, Both Moderate, and Both High). Compared to the Both Low profile, the Both High profile was significantly younger, less likely to be married or partnered, more likely to live alone, had a higher comorbidity burden, and lower functional status. The Both High profile had higher levels of anxiety, depressive symptoms, sleep disturbance, and pain and lower levels of quality of life., Discussion: The variability in the morning and evening severity scores among the four profiles supports the hypothesis that morning and evening fatigue are distinct but related symptoms. Clinically meaningful levels of both morning and evening fatigue were reported by 50.4% of our sample, which suggests that the co-occurrence of these two symptoms is relatively common. Patients in Both Moderate and Both High profiles experienced an extremely high symptom burden that warrants ongoing assessments and aggressive symptom management interventions., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To evaluate differences in the severity of global, cancer-specific, and cumulative life stress, resilience, and common neuropsychological symptoms among four subgroups of patients with distinct chemotherapy-induced nausea (CIN) profiles., Sample & Setting: Adult patients with cancer (N = 1,343) receiving chemotherapy., Methods & Variables: Patients completed stress, resilience, and neuropsychological symptom severity measures. The Memorial Symptom Assessment Scale was used to assess CIN occurrence six times over two cycles of chemotherapy. Parametric and nonparametric statistics were used to evaluate differences among subgroups of patients with distinct CIN profiles., Results: The high class had significantly higher levels of global, cancer-specific, and cumulative life stress; significantly higher levels of depression, anxiety, sleep disturbance, morning and evening fatigue, and pain; and lower levels of morning and evening energy and cognitive dysfunction., Implications for Nursing: Clinicians need to evaluate CIN occurrence across each cycle of chemotherapy and assess patients for various types of stress and common neuropsychological symptoms.

Objectives: To navigate the field of digital cancer care and define and discuss key aspects and applications of big data analytics, artificial intelligence (AI), and data-driven interventions., Data Sources: Peer-reviewed scientific publications and expert opinion., Conclusion: The digital transformation of cancer care, enabled by big data analytics, AI, and data-driven interventions, presents a significant opportunity to revolutionize the field. An increased understanding of the lifecycle and ethics of data-driven interventions will enhance development of innovative and applicable products to advance digital cancer care services., Implications for Nursing Practice: As digital technologies become integrated into cancer care, nurse practitioners and scientists will be required to increase their knowledge and skills to effectively use these tools to the patient's benefit. An enhanced understanding of the core concepts of AI and big data, confident use of digital health platforms, and ability to interpret the outputs of data-driven interventions are key competencies. Nurses in oncology will play a crucial role in patient education around big data and AI, with a focus on addressing any arising questions, concerns, or misconceptions to foster trust in these technologies. Successful integration of data-driven innovations into oncology nursing practice will empower practitioners to deliver more personalized, effective, and evidence-based care., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: A psychological symptom cluster is the most common cluster identified in oncology patients. Although inflammatory mechanisms are hypothesized to underlie this cluster, epigenetic contributions are unknown., Objectives: This study's purpose was to evaluate associations between the occurrence of a psychological symptom cluster and levels of DNA methylation for inflammatory genes in a heterogeneous sample of patients with cancer receiving chemotherapy., Methods: Prior to their second or third cycle of chemotherapy, 1,071 patients reported the occurrence of 38 symptoms using the Memorial Symptom Assessment Scale. A psychological cluster was identified using exploratory factor analysis. Differential methylation analyses were performed in two independent samples using Illumina Infinium 450K and EPIC microarrays. Expression-associated CpG (eCpG) loci in the promoter region of 114 inflammatory genes on the 450K and 112 genes on the EPIC microarray were evaluated for associations with the psychological cluster. Robust rank aggregation was used to identify differentially methylated genes across both samples. Significance was assessed using a false discovery rate of 0.05 under the Benjamini-Hochberg procedure., Results: Cluster of differentiation 40 ( CD40 ) was differentially methylated across both samples. All six promoter eCpGs for CD40 that were identified across both samples were hypomethylated in the psychological cluster group., Conclusions: This study is the first to suggest associations between a psychological symptom cluster and differential DNA methylation of a gene involved in tissue inflammation and cell-mediated immunity. Our findings suggest that increased CD40 expression through hypomethylation of promoter eCpG loci is involved in the occurrence of a psychological symptom cluster in patients receiving chemotherapy. These findings suggest a direction for mechanistic studies., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While pain is a significant problem for oncology patients, little is known about interindividual variability in pain characteristics., Objective: The aims of this study were to identify subgroups of patients with distinct worst pain severity profiles and evaluate for differences among these subgroups in demographic, clinical, and pain characteristics and stress and symptom scores., Methods: Patients (n = 934) completed questionnaires 6 times over 2 chemotherapy cycles. Worst pain intensity was assessed using a 0- to 10-point numeric rating scale. Brief Pain Inventory was used to assess various pain characteristics. Latent profile analysis was used to identify subgroups of patients with distinct pain profiles., Results: Three worst pain profiles were identified (low [17.5%], moderate [39.9%], severe [42.6%]). Compared with the other 2 classes, severe class was more likely to be single and unemployed and had a lower annual household income, a higher body mass index, a higher level of comorbidity, and a poorer functional status. Severe class was more likely to have both cancer and noncancer pain, a higher number of pain locations, higher frequency and duration of pain, worse pain quality scores, and higher pain interference scores. Compared with the other 2 classes, severe class reported lower satisfaction with pain management and higher global, disease-specific, and cumulative life stress, as well as higher anxiety, depression, fatigue, sleep disturbance, and cognitive dysfunction scores., Conclusions: Unrelieved pain is a significant problem for more than 80% of outpatients., Implications for Practice: Clinicians need to perform comprehensive pain assessments; prescribe pharmacologic and nonpharmacologic interventions; and initiate referrals for pain management and psychological services., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Problem Identification: Dyspnea is a common and distressing symptom for patients with cancer. Although the risk factors for dyspnea in patients with cancer are likely to be multifactorial, a comprehensive description of these risk factors and associated mechanisms is not available in the extant literature., Literature Search: A search of all relevant databases, including Cochrane Library, PubMed®, Embase®, Web of Science, and CINAHL®, was done from January 2009 to May 2022. Case-control and cohort studies that had either a cross-sectional or longitudinal design, as well as randomized controlled trials, were included in the review. Peer-reviewed, full-text articles in English were included. Nineteen studies reported on risk factors for dyspnea., Data Evaluation: The methodologic quality of each study was examined using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies., Synthesis: A number of factors can influence the occurrence and severity of dyspnea. Using the Mismatch Theory of Dyspnea as the central core of this Multifactorial Model of Dyspnea in Patients With Cancer, the factors included in this conceptual model are person, clinical, and cancer-related factors, as well as respiratory muscle weakness, co-occurring symptoms, and stress., Implications for Practice: The Multifactorial Model of Dyspnea in Patients With Cancer can be used by clinicians to evaluate for multiple factors that contribute to dyspnea and to develop individualized and multilevel interventions for patients experiencing this symptom.

Introduction: Fatigue is the most common and debilitating symptom experienced by cancer patients undergoing chemotherapy (CTX). Prediction of symptom severity can assist clinicians to identify high-risk patients and provide education to decrease symptom severity. The purpose of this study was to predict the severity of morning fatigue in the week following the administration of CTX., Methods: Outpatients (n = 1217) completed questionnaires 1 week prior to and 1 week following administration of CTX. Morning fatigue was measured using the Lee Fatigue Scale (LFS). Separate prediction models for morning fatigue severity were created using 157 demographic, clinical, symptom, and psychosocial adjustment characteristics and either morning fatigue scores or individual fatigue item scores. Prediction models were created using two regression and five machine learning approaches., Results: Elastic net models provided the best fit across all models. For the EN model using individual LFS item scores, two of the 13 individual LFS items (i.e., "worn out," "exhausted") were the strongest predictors., Conclusions: This study is the first to use machine learning techniques to accurately predict the severity of morning fatigue from prior to through the week following the administration of CTX using total and individual item scores from the Lee Fatigue Scale (LFS). Our findings suggest that the language used to assess clinical fatigue in oncology patients is important and that two simple questions may be used to predict morning fatigue severity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This brief report introduces the Cancer Outcomes and Survivorship domain in the PhenX Toolkit (consensus measures for Phenotypes and eXposures), which includes 15 validated measurement protocols for cancer survivorship research that were recommended for inclusion in this publicly available resource. Developed with input from the scientific community, the domain provides researchers with well-established measurement protocols for evaluating physical and psychological effects, financial toxicity, and patient experiences with cancer care. The PhenX Toolkit, funded by the National Human Genome Research Institute since 2007, is an online resource that provides high-quality standard measurement protocols for a wide range of research areas (eg, smoking cessation, harm reduction and biomarkers, and social determinants of health). Use of the PhenX Cancer Survivorship Outcomes and Survivorship domain can simplify the selection of measurement protocols, data sharing, and comparisons across studies investigating the cancer survivorship experience., (© The Author(s) 2023. Published by Oxford University Press.)

Context: Shortness of breath is a distressing symptom that occurs in 10% to 70% of oncology patients. Despite this broad range in its occurrence, little is known about inter-individual variability in shortness of breath and associated risk factors among patients receiving chemotherapy., Objectives: Identify subgroups of patients with distinct shortness of breath profiles; evaluate for differences among these subgroups in demographic and clinical characteristics; evaluate for differences among symptom dimensions of shortness of breath, and evaluate for differences in quality of life outcomes., Methods: Outpatients (n=1338) completed questionnaires six times over two chemotherapy cycles. Occurrence of shortness of breath was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups of patients with distinct shortness of breath profiles., Results: Four distinct shortness of breath profiles were identified (None [70.5%], Decreasing [8.2%], Increasing [7.8%], High [13.5%]). Risk factors for membership in High class included: history of smoking, self-reported diagnosis of lung disease, having lung cancer, and receipt of a higher number of cancer treatments. Compared to the None class, High class reported poorer physical, psychological, and social functioning., Conclusions: Almost 14% of patients with heterogeneous types of cancer receiving chemotherapy had persistently high occurrence rates of shortness of breath for almost two months. In addition, compared to the Decreasing and Increasing classes, the High class' episodes of shortness of breath were more frequent and more severe. Clinicians need to assess all oncology patients for shortness of breath and provide targeted interventions., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Moderate to severe fatigue occurs in up to 94% of patients with cancer. Recent evidence suggests that morning and evening fatigue are distinct dimensions of physical fatigue. The purposes of this study were to evaluate the transcriptome for common and distinct perturbed inflammatory pathways in patients receiving chemotherapy who reported low versus high levels of morning or low versus high levels of evening cancer-related fatigue., Methods: Patients completed questionnaires during the week prior to their chemotherapy treatment. Severity of morning and evening fatigue was evaluated using the Lee Fatigue Scale. Gene expression and pathway impact analyses (PIA) were performed in two independent samples using RNA-sequencing (n = 357) and microarray (n = 360). Patterns of interactions between and among these perturbed pathways were evaluated using a knowledge network (KN)., Results: Across the PIA, nine perturbed pathways (FDR < 0.025) were common to both morning and evening fatigue, six were distinct for morning fatigue, and four were distinct for evening fatigue. KN (19 nodes, 39 edges) identified the phosphatidylinositol 3-kinase (PI3K)-Akt pathway node (perturbed in evening fatigue) with the highest betweenness (0.255) and closeness (0.255) centrality indices. The next highest betweenness centrality indices were seen in pathways perturbed in evening fatigue (i.e., nuclear factor kappa B: 0.200, natural killer cell-mediated cytotoxicity: 0.178, mitogen-activated protein kinase: 0.175)., Conclusions: This study describes perturbations in common and distinct inflammatory pathways associated with morning and/or evening fatigue. PI3K-Akt was identified as a bottleneck pathway. The analysis identified potential targets for therapeutic interventions for this common and devastating clinical problem., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Context: Cognitive and physical fatigue are common symptoms experienced by oncology patients. Exposure to stressful life events (SLE), cancer-related stressors, coping styles, and levels of resilience may influence the severity of both dimensions of fatigue., Objectives: Evaluate for differences in global, cancer-specific, and cumulative life stress, as well as resilience and coping in oncology patients (n=1332) with distinct cognitive fatigue AND evening physical fatigue profiles., Methods: Latent profile analysis, which combined the two symptom scores, identified three subgroups of patients with distinct cognitive fatigue AND evening physical fatigue profiles (i.e., Low, Moderate, High). Patients completed measures of global, cancer-specific, and cumulative life stress as well measures of resilience and coping. Differences among the latent classes in the various measures were evaluated using parametric and nonparametric tests., Results: Compared to Low class, the other two classes reported higher global and cancer-specific stress. In addition, they reported higher occurrence rates for sexual harassment and being forced to touch prior to 16 years of age. Compared to the other two classes, High class reported lower resilience scores and higher use of denial, substance use, and behavioral disengagement., Conclusion: To decrease both cognitive and evening physical fatigue, clinicians need to assess for relevant stressors and initiate interventions to increase resilience and the use of engagement coping strategies. Additional research is warranted on the relative contribution of various social determinants of health to both cognitive and physical fatigue in oncology patients receiving chemotherapy., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to declare., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Unrelieved chemotherapy-induced nausea (CIN) occurs 48% of patients undergoing chemotherapy and is one of the most debilitating symptoms that patients report., Objective: The aims of this study were to identify subgroups of patients with distinct CIN profiles and determine how these subgroups differed on demographic and clinical characteristics; severity, frequency, and distress of CIN; and the co-occurrence of common gastrointestinal symptoms., Methods: Patients (n = 1343) completed demographic questionnaire and Memorial Symptom Assessment Scale 6 times over 2 cycles of chemotherapy. Latent class analysis was used to identify subgroups of patients with distinct CIN profiles. Differences among these subgroups were evaluated using parametric and nonparametric statistics., Results: Four distinct CIN profiles were identified: none (40.8%), increasing-decreasing (21.5%), decreasing (8.9%), and high (28.8%). Compared with the none class, patients in the high class were younger, had a lower annual household income, had child care responsibilities, had a lower Karnofsky Performance Status score and a higher Self-administered Comorbidity Questionnaire score, and were more likely to have received chemotherapy on a 14-day cycle and a highly emetogenic chemotherapy regimen. In addition, patients in the high class reported high occurrence rates for dry mouth, feeling bloated, diarrhea, lack of appetite, abdominal cramps, difficulty swallowing, mouth sores, weight loss, and change in the way food tastes., Conclusions: That 60% of the patients reported moderate to high CIN occurrence rates confirms that this unrelieved symptom is a significant clinical problem., Implications for Practice: Nurses need to evaluate patients' level of adherence to their antiemetic regimen and make appropriate referrals for physical therapy, psychological services, and dietary counseling., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Problem Identification: Cancer-related cognitive impairment (CRCI) is common and is associated with cancer and its treatments. Evidence suggests that the causes are multifactorial, but the field is lacking a comprehensive conceptual model of CRCI to summarize existing knowledge and provide a way to understand and predict causal links, as well as to generate hypotheses., Literature Search: PubMed® and Google Scholar™ were searched, and 130 articles demonstrated several lacking factors needed for a more comprehensive CRCI model., Data Evaluation: The new multifactorial model of CRCI includes social determinants of health, patient-specific factors, co-occurring symptoms, treatment factors, and biologic mechanisms., Synthesis: The multifactorial model of CRCI is based on established and emerging evidence. This model is inclusive of all cancer types and associated treatments., Implications for Nursing: Although it would be ideal to evaluate all the concepts and components in this model in a comprehensive fashion, investigators with existing datasets could evaluate portions of the model to determine directionality for some of the proposed relationships. The new model can be used to design preclinical and clinical studies of CRCI. Knowledge of the occurrence of CRCI and factors that contribute to this symptom will allow nurses to perform assessments of modifiable and nonmodifiable risk factors.

Purpose: Evaluate for differences in demographic and clinical characteristics, occurrence of common symptoms, symptom severity scores, and quality of life (QOL) outcomes in survivors with (n = 155) and without (n = 118) audiometrically confirmed hearing loss., Methods: Survivors, who were recruited from throughout the San Francisco Bay area, completed the self-report questionnaires to obtain the information of demographic and clinical characteristics; the occurrence and severity of depression, anxiety, fatigue, decrements in energy, sleep disturbance, pain, and cognitive impairment; and the general and cancer-specific QOL outcomes. Parametric and non-parametric tests were used to evaluate for differences between the two survivor groups., Results: Survivors with audiometrically confirmed hearing loss were older, more likely to be male, were more likely to be unemployed, report a lower annual household income, and had a higher comorbidity burden. Except for the severity of worst pain, no between-group differences were found in the occurrence rates for or severity of any of the symptoms. Survivors with hearing loss reported worse physical function and general health scores., Conclusions: While no between-group differences in symptom occurrence rates and severity scores were found, across the total sample, a relatively high percentage of survivors who were over 6 years from their cancer diagnosis reported clinically meaningful levels of depression (25%), anxiety (50%), fatigue (40%), decrements in energy (70%), sleep disturbance (58%), cognitive impairment (57%), and pain (60%)., Implications for Cancer Survivors: Clinicians need to perform routine assessments of hearing loss, as well as common co-occurring symptoms and initiate individualized symptom management interventions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Unrelieved pain occurs in 55% of cancer patients. Identification of molecular mechanisms for pain may provide insights into therapeutic targets. Purpose was to evaluate for perturbations in neuroinflammatory pathways between oncology patients with and without severe pain. Worst pain severity was rated using a 0 to 10 numeric rating scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct pain profiles. Pathway impact analyses were performed in two independent samples using gene expression data obtained from RNA sequencing (n = 192) and microarray (n = 197) technologies. Fisher's combined probability test was used to identify significantly perturbed pathways between None versus the Severe pain classes. In the RNA sequencing and microarray samples, 62.5% and 56.3% of patients were in the Severe pain class, respectively. Nine perturbed pathways were related to neuroinflammatory mechanisms (i.e., retrograde endocannabinoid signaling, gamma-aminobutyric acid synapse, glutamatergic synapse, Janus kinase-signal transducer and activator of transcription signaling, phagosome, complement and coagulation cascades, cytokine-cytokine receptor interaction, chemokine signaling, calcium signaling). First study to identify perturbations in neuroinflammatory pathways associated with severe pain in oncology outpatients. Findings suggest that complex neuroimmune interactions are involved in the maintenance of chronic pain conditions. Perspective: In this study that compared oncology patients with none versus severe pain, nine perturbed neuroinflammatory pathways were identified. Findings suggest that complex neuroimmune interactions are involved in the maintenance of persistent pain conditions., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Patients undergoing cancer treatment experience global stress and cancer-specific stress. Both types of stress are associated with a higher symptom burden., Objective: In this cross-sectional study, we used a comprehensive set of demographic, clinical, and symptom characteristics to evaluate their relative contribution to the severity of global and cancer-specific stress., Methods: Patients (N = 941) completed study questionnaires before their second or third cycle of chemotherapy., Results: Consistent with our a priori hypothesis, we found both common and distinct characteristics associated with higher levels of global stress and cancer-specific stress. A significant proportion of our patients had scores on the Impact of Event Scale-Revised suggestive of subsyndromal (29.4%) or probable (13.9%) posttraumatic stress disorder. Four of the 5 stepwise linear regression analyses for the various stress scales explained between 41.6% and 54.5% of the total variance. Compared with various demographic and clinical characteristics, many of the common symptoms associated with cancer and its treatments uniquely explained a higher percentage of the variance in the various stress scales. Symptoms of depression made the largest unique contribution to the percentage of total explained variance across all 5 scales., Conclusion: Clinicians need to assess for global stress, cancer-specific stress, and depression in patients receiving chemotherapy., Implications for Practice: Patients may benefit from integrative interventions (eg, mindfulness-based stress reduction, cognitive behavioral therapy, acupuncture) that simultaneously address stress and symptoms commonly associated with cancer and its treatments., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective/background: Sleep disturbance is a common problem in patients receiving chemotherapy. Purpose was to evaluate for perturbations in immune-inflammatory pathways between oncology patients with low versus very high levels of sleep disturbance., Patients/methods: Sleep disturbance was evaluated using the General Sleep Disturbance Scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct sleep disturbance profiles. Pathway impact analyses were performed in two independent samples using gene expression data obtained from RNA sequencing (n = 198) and microarray (n = 162) technologies. Fisher's combined probability test was used to identify significantly perturbed pathways between Low versus Very High sleep disturbance classes., Results: In the RNA sequencing and microarray samples, 59.1% and 51.9% of patients were in the Very High sleep disturbance class, respectively. Thirteen perturbed pathways were related to immune-inflammatory mechanisms (i.e., endocytosis, phagosome, antigen processing and presentation, natural killer cell mediated cytotoxicity, cytokine-cytokine receptor interaction, apoptosis, neutrophil extracellular trap formation, nucleotide-binding and oligomerization domain-like receptor signaling, Th17 cell differentiation, intestinal immune network for immunoglobulin A production, T-cell receptor signaling, complement and coagulation cascades, and tumor necrosis factor signaling)., Conclusions: First study to identify perturbations in immune-inflammatory pathways associated with very high levels of sleep disturbance in oncology outpatients. Findings suggest that complex immune-inflammatory interactions underlie sleep disturbance., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: While the gastrointestinal symptom cluster (GISC) is common in patients receiving chemotherapy, limited information is available on its underlying mechanism(s). Emerging evidence suggests a role for inflammatory processes through the actions of the nuclear factor kappa B (NF-κB) signaling pathway. This study evaluated for associations between a GISC and levels of DNA methylation for genes within this pathway., Methods: Prior to their second or third cycle of chemotherapy, 1071 outpatients reported symptom occurrence using the Memorial Symptom Assessment Scale. A GISC was identified using exploratory factor analysis. Differential methylation analyses were performed in two independent samples using EPIC ( n = 925) and 450K ( n = 146) microarrays. Trans expression-associated CpG (eCpG) loci for 56 NF-κB signaling pathway genes were evaluated. Loci significance were assessed using an exploratory false discovery rate (FDR) of 25% for the EPIC sample. For the validation assessment using the 450K sample, significance was assessed at an unadjusted p -value of 0.05., Results: For the EPIC sample, the GISC was associated with increased expression of lymphotoxin beta ( LTB ) at one differentially methylated trans eCpG locus (cg03171795; FDR = 0.168). This association was not validated in the 450K sample., Conclusions: This study is the first to identify an association between a GISC and epigenetic regulation of a gene that is involved in the initiation of gastrointestinal immune responses. Findings suggest that increased LTB expression by hypermethylation of a trans eCpG locus is involved in the occurrence of this cluster in patients receiving chemotherapy. LTB may be a potential therapeutic target for this common cluster.

Background: Dyspnea is a common and distressing symptom for oncology patients.However, dyspnea is not well-characterized and often underestimated by clinicians. This systematic review summarizes the prevalence, intensity, distress, and impact of dyspnea in oncology patients and identifies research gaps., Methods: A search of all of the relevant databases was done from 2009 to May 2022. A qualitative synthesis of the extant literature was performed using established guidelines., Results: One hundred-seventeen studies met inclusion criteria. Weighted grand mean prevalence of dyspnea in patients with advanced cancer was 58.0%. Intensity of dyspnea was most common dimension evaluated, followed by the impact and distress. Depression and anxiety were the most common symptoms that co-occurred with dyspnea., Conclusion: Numerous methodologic challenges were evident across studies. Future studies need to use valid and reliable measures; evaluate the impact of dyspnea; and determine biomarkers for dyspnea., Competing Interests: Conflicts of interest Dr. Wong reported conflicts of interest outside of the submitted work: An immediate family member is an employee of Genentech with stock ownership and Dr. Wong receives royalties from UpToDate. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Patients undergoing chemotherapy for cancer often experience heightened anxiety. While receipt of chemotherapy occurs over multiple cycles, limited research has examined anxiety longitudinally. The purposes of this study, in a large sample of patients with breast, gynecological, gastrointestinal, or lung cancer, were to evaluate, over the course of two cycles of chemotherapy, for inter-individual differences in the trajectories of anxiety and identify associations between demographic, clinical, symptom, and psychological adjustment characteristics and initial levels and trajectories of anxiety., Methods: Patients with breast, gynecologic, lung, or gastrointestinal cancer (n = 1323) were assessed with the Spielberger State Anxiety Inventory (STAI-S) six times over two cycles of chemotherapy. At enrollment, patients completed self-report instruments assessing demographic, symptom, stress, and coping characteristics. We used hierarchical linear modeling to identify risk factors associated with initial levels and trajectories of state anxiety., Results: Inter-individual differences in initial levels of anxiety were associated with functional status, sleep disturbance, morning fatigue, cognitive function, global and cancer-specific stress, resilience, and several coping characteristics (i.e., sense of coherence, acceptance, using emotional support, self-distraction, denial, venting, and self-blame). Demographic and clinical characteristics associated with interindividual differences in anxiety trajectories were age, employment status, and MAX-2 score., Conclusion: This study provides novel data on the course and predictors of anxiety during two cycles of chemotherapy among a large sample of patients with varied cancer types. Further research focused on risk factors for heightened levels of anxiety during chemotherapy may help point toward more effective interventions for this commonly experienced symptom., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)