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PurposeEvaluate 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.MethodsAdult 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.ResultsIn 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.ConclusionsFindings 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.

BackgroundAnxiety and sleep disturbance are frequent symptoms during chemotherapy.ObjectivesPurposes were to identify subgroups of oncology outpatients with distinct joint anxiety and sleep disturbance profiles, as well as evaluate for differences in demographic and clinical characteristics, sleep disturbance characteristics, severity of common symptoms, and quality-of-life outcomes among these subgroups.MethodsOncology outpatients (n = 1331) completed self-report measures of anxiety and sleep disturbance 6 times over 2 chemotherapy cycles. Latent profile analysis was done to identify subgroups of patients with distinct joint anxiety and sleep disturbance profiles.ResultsThree profiles were identified (ie, no anxiety and low sleep disturbance (59.7%), moderate anxiety and high sleep disturbance (32.5%), high anxiety and very high sleep disturbance (7.8%)). Compared with the no anxiety and low sleep disturbance class, the other 2 classes were younger; less likely to be married; had a lower annual household income; and had childcare responsibilities. Patients in the 2 worse profiles had problems with both sleep initiation and maintenance. These patients reported higher levels of depressive symptoms, trait and state anxiety, and evening fatigue, as well as lower levels of morning and evening energy, cognitive function, and poorer quality of life.ConclusionsMore than 40% of patients had moderate or high levels of anxiety and high or very high levels of sleep disturbance. Modifiable risk factors associated with these profiles may be used to develop targeted interventions for 1 or both symptoms.Implications for practiceClinicians need to assess for the co-occurrence of anxiety and sleep disturbance.

BackgroundCancer-related cognitive impairment (CRCI) is a common symptom in patients with breast cancer. In our previous study of 397 women with breast cancer, we identified 3 groups of patients with distinct CRCI profiles (ie, high, moderate, and low-moderate attentional function). Compared with the other 2 classes, the low-moderate class was younger, had more comorbidities, and with lower functional status.ObjectivesIn this study, we expand on this work and evaluate for differences among these latent classes in the severity of psychological (depression and anxiety) and physical (fatigue, decrements in energy, sleep disturbance, and pain) symptoms before surgery.MethodsCancer-related cognitive impairment was assessed using the Attentional Functional Index from before through 6 months after surgery. Lower Attentional Functional Index scores indicate higher levels of CRCI. Psychological and physical symptoms were assessed with valid instruments. Parametric and nonparametric tests were used to evaluate for differences in symptom severity scores among the latent classes.ResultsApproximately 60% of patients experienced CRCI (ie, moderate and low-moderate classes). Significant differences were found among the 3 classes in the severity of trait and state anxiety, depressive symptoms, fatigue, and sleep disturbance (ie, high < moderate < low-moderate). In addition, compared with the other 2 classes, the low-moderate class reported higher pain interference scores.ConclusionsThese findings suggest that women with clinically meaningful levels of persistent CRCI have a relatively high symptom burden before surgery.Implications for practiceClinicians need to routinely perform preoperative assessments of CRCI and associated symptoms and initiate therapeutic interventions.

BackgroundWhile pain is a significant problem for oncology patients, little is known about interindividual variability in pain characteristics.ObjectiveThe 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.MethodsPatients (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.ResultsThree 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.ConclusionsUnrelieved pain is a significant problem for more than 80% of outpatients.Implications for practiceClinicians need to perform comprehensive pain assessments; prescribe pharmacologic and nonpharmacologic interventions; and initiate referrals for pain management and psychological services.

ContextCognitive 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.ObjectivesEvaluate 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.MethodsLatent 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.ResultsCompared 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.ConclusionTo 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.

BackgroundUnrelieved chemotherapy-induced nausea (CIN) occurs 48% of patients undergoing chemotherapy and is one of the most debilitating symptoms that patients report.ObjectiveThe 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.MethodsPatients (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.ResultsFour 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.ConclusionsThat 60% of the patients reported moderate to high CIN occurrence rates confirms that this unrelieved symptom is a significant clinical problem.Implications for practiceNurses need to evaluate patients' level of adherence to their antiemetic regimen and make appropriate referrals for physical therapy, psychological services, and dietary counseling.

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.

Objective/backgroundSleep 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/methodsSleep 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.ResultsIn 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).ConclusionsFirst 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.

PurposeStudy purposes were to evaluate for inter-individual variability in the trajectories of three objective measures of physical function (PF) in older patients receiving chemotherapy (n = 112) and determine which characteristics were associated with worse PF.MethodsBalance, gait speed, and chair-stand test were evaluated at initiation and 1, 3, 6, 9, and 12 months following chemotherapy. Hierarchical linear modeling was used to assess inter-individual variability in the trajectories of the three tests. Demographic, clinical, and symptom characteristics, and levels of cognitive function associated with initial levels and changes over time in each of the tests were determined.ResultsGait speed and chair-stand tests improved over time. Balance declined until month 6, then increased. Characteristics associated with decreases in balance scores at initiation of chemotherapy were lower level of education and lower Karnofsky Performance Status (KPS) score. For initial levels of poorer gait speed, older age, poorer Trail Making Test B (TMTB), and worse Attentional Function Index scores were the associated characteristics. Lower KPS scores, higher body mass index, and poorer TMTB scores were associated with poorer chair-stand times at initiation of chemotherapy. Worse trajectories of chair-stand times were associated with poorer chair-stand time at enrollment. Characteristic associated with lower initial levels and improved trajectories of balance was older age at enrollment.ConclusionsDetermination of characteristics associated with decrements in balance, gait speed, and chair-stand can assist clinicians to identify older oncology patients at risk for decrements in PF. Interventions to maintain and improve PF need to be implemented with higher risk patients.

BackgroundPatients with gynecologic cancer undergoing chemotherapy experience multiple co-occurring symptoms. Understanding how symptom clusters change over time is essential to the development of interventions that target multiple co-occurring symptoms.ObjectiveThe aim of this study was to assess the relative stability of symptom clusters across a chemotherapy cycle in patients with gynecologic cancer.MethodsThis is a longitudinal, descriptive study. Eligible patients (n = 232) were English-speaking adults (≥18 years old) with gynecologic cancer. Data were collected in the week before patients' second or third cycle of chemotherapy (T1) and at 1 (T2) and 2 (T3) weeks after chemotherapy. Three dimensions of the symptom experience (occurrence, severity, and distress) were assessed using a modified version of the Memorial Symptom Assessment Scale. Symptom clusters for each dimension and time point were identified through exploratory factor analysis.ResultsA 5-factor solution was selected for each exploratory factor analysis. Hormonal, respiratory, and weight change clusters were identified across all dimensions and time points. A psychological symptom cluster was identified at T1 for occurrence and severity and at T2 and T3 for all 3 dimensions. A gastrointestinal symptom cluster was identified at T1 for occurrence and at T2 and T3 for all 3 dimensions. The hormonal, respiratory, psychological, and weight change symptom clusters exhibited common symptoms across dimensions and time points.ConclusionsHormonal, respiratory, weight change, and psychological symptom clusters are relatively stable across a cycle of chemotherapy in patients with gynecologic cancer.Implications for practiceClinicians need to assess patients for multiple co-occurring symptoms and initiate multimodal interventions.

PurposeIn a sample of oncology patients, identify subgroups of patients with distinct depressive symptom profiles and evaluate for differences in demographic and clinical characteristics, levels of stress and resilience, and the severity of common co-occurring symptoms.MethodsPatients (n = 1327) 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. Demographic and clinical characteristics, stress, resilience, and co-occurring symptoms were evaluated at enrollment. Depressive symptoms were evaluated using the Center for Epidemiological Studies-Depression (CES-D) scale a total of six times over two cycles of chemotherapy. Latent profile analysis (LPA) was used to identify subgroups of patients (i.e., latent classes) with distinct depressive symptom profiles using the six CES-D scores.ResultsBased on the findings from the LPA, 47.3% of the patients were classified as "None"; 33.6% as "Subsyndromal"; 13.8% as "Moderate"; and 5.3% as "High". Compared to None class, patients in the Subsyndromal, Moderate, and High classes had a lower functional status, a higher comorbidity burden, and a self-reported diagnosis of depression or back pain. Those patients with higher levels of depressive symptoms reported higher levels of stress, lower levels of resilience, and increased severity of co-occurring symptoms.ConclusionsInter-individual variability in depressive symptoms was associated with demographic and clinical characteristics, multiple types of stress and levels of resilience, as well as with the increased severity of multiple co-occurring symptoms. The risk factors associated with worse depressive symptom profiles can assist clinicians to identify high risk patients and initiate more timely supportive care interventions.

BackgroundUnrelieved chemotherapy-induced nausea (CIN) is a significant problem for patients with breast cancer (BC).ObjectiveIn a sample of patients with BC who were assessed before their second or third cycle of chemotherapy, study purposes were to evaluate for the occurrence, severity, frequency, and distress associated with CIN; evaluate for differences in demographic and clinical characteristics and gastrointestinal (GI) symptom occurrence rates between patients who did and did not report CIN; and determine which demographic, clinical, and symptom characteristics were associated with the occurrence of CIN.MethodsPatients completed demographic and clinical questionnaires and the Memorial Symptom Assessment Scale for nausea and common GI symptom assessments. Univariate analyses evaluated for differences in demographic and clinical characteristics and GI symptom occurrence between patients who did and did not report CIN. Multiple logistic regression analysis evaluated for characteristics associated with CIN.ResultsOf the 532 patients with BC, 47.2% reported CIN occurrence. Characteristics associated with CIN group membership were poorer functional status, receipt of chemotherapy on a 14-day cycle, and higher occurrence rates of 5 GI symptoms (ie, dry mouth, vomiting, constipation, change in the way food tastes, and lack of appetite; all P < .001).ConclusionsUnrelieved CIN is a common symptom in patients with BC. This study is the first to demonstrate that 5 co-occurring GI symptoms were associated with CIN occurrence.Implications for practiceThis study identified new risk factors for CIN occurrence in patients with BC. Clinicians may be able to initiate additional interventions to alleviate CIN.

Background: Lymphedema (LE) is a significant clinical problem for breast cancer survivors. While the water displacement test and circumferential assessment using a tape measure (TM) are common methods to assess differences in arm volumes, faster and more reliable methods are needed. Study purposes, in breast cancer survivors (n = 294), were to compare the average total arm volumes and interlimb volume ratios for women with and without a history of LE, using a TM and three-dimensional (3D), whole-body surface scanner (3D scan); compare the level of agreement between arm volumes and interlimb volume ratios obtained using the two devices; and evaluate the percent agreement between the two measures in classifying cases of LE using three accepted thresholds. Methods and Results: Measurements were done using a spring-loaded TM and Fit3D ProScanner. Paired t-tests and Bland-Altman analyses were used to achieve the study aims. For circumference and volume comparisons, compared with the 3D scan, values obtained using the TM were consistently smaller. In terms of level of agreement, the Bland-Altman analyses demonstrated large biases and wide limits of agreement for the calculated arm volumes and volume ratios. In terms of the classification of caseness, using the 200-mL interlimb volume difference criterion resulted in 81.6% overall agreement; using the >10% volume difference between the affected and unaffected arms resulted in 78.5% overall agreement; and using the volume ratio ≥1.04 criterion resulted in 62.5% overall agreement. For all three accepted threshold criteria, the percentage of cases was significantly different between the TM and 3D scan techniques. Conclusions: The 3D technology evaluated in this study has the potential to be used for self-initiated surveillance for LE. With improvements in landmark identification and software modifications, it is possible that accurate and reliable total arm volumes can be calculated and used for early detection.

ContextCutpoints can be used as a threshold for screening symptom(s) that warrant intervention(s) and for monitoring patients' responses to these interventions.ObjectivesIn a sample of oncology patients undergoing chemotherapy, study purposes were to determine the optimal cutpoints for low, moderate, and high symptom burden and determine if these cutpoints distinguished among the symptom groups in any demographic, clinical, and stress characteristics, as well as QOL outcomes.MethodsTotal of 1329 patients completed a modified version of the Memorial Symptom Assessment Scale (38 symptoms). Using the methodology of Serlin and colleagues, cutpoints were created using symptom occurrence rates and cancer-specific quality of life (QOL) scores. Cutpoints were validated using measures of stress and resilience and a generic measure of QOL (i.e., Medical Outcomes Study Short Form 12 (SF-12)).ResultsOf the 25 possible cutpoints evaluated, the optimal cutpoint, with the largest between category F statistic, was CP8,15 (Low = 0-8, Moderate = 9-15, High = 16-38 symptoms). Percentage of patients in the Low, Moderate, and High cutpoint groups were 25.3%, 36.3%, and 38.4%, respectively. Significant differences were found among the symptom burden groups in global, cancer-specific, and cumulative life stress (i.e., Low < Moderate < High) and resilience and SF-12 (i.e., Low > Moderate > High) scores.ConclusionOur findings provide evidence for clinically meaningful cutpoints that can be used to guide symptom assessment and management. These cutpoints may be used to establish alert thresholds for electronic monitoring of symptoms in oncology patients.

Little is known about the associations between pain, stress, and co-occurring symptoms in oncology patients. Purpose was to identify subgroups of patients with distinct worst pain profiles and evaluate for differences among the subgroups in demographic and clinical characteristics, as well as stress and symptom scores. Oncology outpatients (n = 1305) completed questionnaires prior to their second or third chemotherapy cycle. Worst pain intensity was assessed 6 times over 2 chemotherapy cycles using a 0 to 10 numeric rating scale. The 371 patients (28.4%) who had ≤1 occurrence of pain over the 6 assessments were classified as the None class. For the remaining 934 patients whose data were entered into the latent profile analysis, 3 distinct worst pain profiles were identified (ie Mild [12.5%], Moderate [28.6%], Severe [30.5%]). Compared to None class, Severe class had fewer years of education and a lower annual income; were less likely to be employed and married; less likely to exercise on a regular basis, had a higher comorbidity burden, and a worse functional status. Compared to None class, Severe class reported higher levels of general, disease-specific, and cumulative life stress and lower levels of resilience, as well as higher levels of depressive symptoms, anxiety, fatigue, sleep disturbance, and cognitive dysfunction. This study is the first to identify distinct worst pain profiles in a large sample of oncology patients receiving chemotherapy and associated risk factors. PERSPECTIVE: Unrelieved pain remains a significant problem for oncology patients receiving chemotherapy. High levels of stress and co-occurring symptoms contribute to a more severe pain profile in these patients.

Cancer related cognitive impairment (CRCI) is a common and persistent symptom in breast cancer patients. The Attentional Function Index (AFI) is a self-report measure that assesses CRCI. AFI includes three subscales, namely effective action, attentional lapses, and interpersonal effectiveness, that are based on working memory, inhibitory control, and cognitive flexibility. Previously, we identified three classes of patients with distinct CRCI profiles using the AFI total scores. The purpose of this study was to expand our previous work using latent class growth analysis (LCGA), to identify distinct cognitive profiles for each of the AFI subscales in the same sample (i.e., 397 women who were assessed seven times from prior to through to 6 months following breast cancer surgery). For each subscale, parametric and non-parametric statistics were used to determine differences in demographic, clinical, and pre-surgical psychological and physical symptoms among the subgroups. Three-, four-, and two-classes were identified for the effective action, attentional lapses, and interpersonal effectiveness subscales, respectively. Across all three subscales, lower functional status, higher levels of anxiety, depression, fatigue, and sleep disturbance, and worse decrements in energy were associated with worse cognitive performance. These and other modifiable characteristics may be potential targets for personalized interventions for CRCI.

PurposeThe purposes of this study, in a sample of oncology patients (n = 1326) receiving chemotherapy, were to identify subgroups of patients with distinct anxiety profiles and evaluate for differences in demographic and clinical characteristics, stress and resilience measures, and severity of co-occurring symptoms (i.e., depression, sleep disturbance, attentional function, fatigue, pain).MethodsPatients completed self-report questionnaires a total of six times over two cycles of chemotherapy. Severity of state anxiety was evaluated using the Spielberger State Anxiety Inventory and resilience was assessed using the Connor-Davidson Resilience Scale. Symptoms were assessed using the Center for Epidemiologic Studies Depression Scale, General Sleep Disturbance Scale, Lee Fatigue Scale, Attentional Function Index and Brief Pain Inventory.ResultsBased on the findings from the latent profile analysis that utilized the six assessments of state anxiety, 47.7% of the patients were classified as "Low," 28.3% as "Moderate," 19.5% as "High," and 4.5.% as "Very High." Anxiety levels remained relatively stable across the six timepoints. Compared to the Low class, membership in the Moderate, High, and Very High classes was associated with a number of characteristics (e.g., younger age, female gender, lower functional status, more comorbidities). Those patients with higher levels of anxiety reported higher levels of stress, lower levels of resilience, and increased severity of co-occurring symptoms.ConclusionOur findings suggest that a substantial number of oncology patients may warrant referral to psychological services. Clinicians need to perform systematic assessments of anxiety, stress, and common symptoms and initiate appropriate interventions to enhance resilience and coping.

Cancer-related cognitive impairment (CRCI) is a significant problem for patients receiving chemotherapy. While a growing amount of pre-clinical and clinical evidence suggests that inflammatory mechanisms underlie CRCI, no clinical studies have evaluated for associations between CRCI and changes in gene expression. Therefore, the purpose of this study was to evaluate for differentially expressed genes and perturbed inflammatory pathways across two independent samples of patients with cancer who did and did not report CRCI. The Attentional Function Index (AFI) was the self-report measure used to assess CRCI. AFI scores of 7.5 indicate low versus high levels of cognitive function, respectively. Of the 185 patients in Sample 1, 49.2% had an AFI score of 7.5. Of the 158 patients in Sample 2, 50.6% had an AFI score of 7.5. Data from 182 patients in Sample 1 were analyzed using RNA-seq. Data from 158 patients in Sample 2 were analyzed using microarray. Twelve KEGG signaling pathways were significantly perturbed between the AFI groups, five of which were signaling pathways related to inflammatory mechanisms (e.g., cytokine-cytokine receptor interaction, tumor necrosis factor signaling). This study is the first to describe perturbations in inflammatory pathways associated with CRCI. Findings highlight the role of cytokines both in terms of cytokine-specific pathways, as well as pathways involved in cytokine production and cytokine activation. These findings have the potential to identify new targets for therapeutics and lead to the development of interventions to improve cognition in patients with cancer.

Background: While supine bioimpedance devices are used to evaluate for lymphedema (LE), stand-on devices are gaining popularity. Because research on differences in bioimpedance values between the two devices is limited, this study's purposes were to: (1) determine the average upper limb impedance values and inter-limb ratios for women who self-reported having (n = 34) or not having (n = 61) a history of LE, using a single-frequency supine device and a multifrequency stand-on device; (2) compare the level of agreement in inter-limb impedance ratios between the two devices; evaluate the percent agreement between the two devices in classifying cases of LE using established supine thresholds; and evaluate the percent agreement in classifying cases of LE between the supine device using previously established supine thresholds and the stand-on device using two published standing thresholds. Methods and Results: Bioimpedance measures were done using the two devices. For the entire sample, absolute impedance values for both the affected and unaffected limbs were significantly higher for the stand-on device in women with and without LE. Impedance values for the two methods were highly correlated. Bland-Altman analysis determined that for the entire range of impedance ratios the values for the two devices could not be used interchangeably. Conclusions: Findings suggest that the stand-on device can be a useful and valid tool to assess for LE. However, because agreement is not perfect, values obtained from the two devices should not be used interchangeably to evaluate for changes in impedance ratios, particularly for ratios of >1.20.

PurposeTo identify subgroups of female breast cancer patients with distinct self-reported employment interference (EI) profiles and determine which demographic, clinical, and symptom characteristics, and quality of life outcomes were associated with subgroup membership.MethodsWomen with breast cancer (n = 385) were assessed for changes in EI over ten times, from prior to, through 12 months after breast cancer surgery. Latent profile analysis (LPA) was used to identify subgroups of patients with distinct EI profiles.ResultsThree distinct EI profiles (i.e., None - 26.2% (n = 101), Low - 42.6% (n = 164), High - 31.2% (n = 120)) were identified. Compared to the None and Low groups, patients in the High group were more likely to be younger. Higher proportions in the High group were non-White, pre-menopausal prior to surgery, had more advanced stage disease, had received an axillary lymph node dissection, had received neoadjuvant chemotherapy, had received adjuvant chemotherapy, and had a re-excision or mastectomy on the affected breast within 6 months after surgery. In addition, these patients had lower quality of life scores. Compared to the None group, the High group had higher levels of trait and state anxiety, depressive symptoms, fatigue and sleep disturbance and lower levels of cognitive function.ConclusionsThis study provides new knowledge regarding EI profiles among women in the year following breast cancer surgery. The non-modifiable risk factors (e.g., younger age, being non-White, having more advanced stage disease) can inform current screening procedures. The potentially modifiable risk factors can be used to develop interventions to improve employment outcomes of breast cancer patients.

BackgroundLoneliness and social isolation are significant public health problems that are being exacerbated during the coronavirus disease 2019 pandemic. Little is known about the associations between loneliness and symptom burden in oncology patients before and during the pandemic. Study purposes include determining the prevalence of loneliness in a sample of oncology patients; evaluating for differences in demographic, clinical, and symptom characteristics between lonely and nonlonely patients; and determining which demographic, clinical, and symptom characteristics were associated with membership in the lonely group.MethodsA convenience sample (n = 606) completed online surveys that evaluated the severity of loneliness, social isolation, and common symptoms (ie, anxiety, depression, fatigue, sleep disturbance, cognitive dysfunction, and pain) in oncology patients. Parametric and nonparametric tests were used to evaluate for differences in scores between the lonely and nonlonely groups. Logistic regression analysis was used to determine risk factors for membership in the loneliness group.ResultsOf the 606 patients, 53.0% were categorized in the lonely group. The lonely group reported higher levels of social isolation, as well as higher symptom severity scores for all of the symptoms evaluated. In the multivariate model, being unmarried, having higher levels of social isolation, as well as higher levels of anxiety and depressive symptoms were associated with membership in the lonely group.ConclusionsStudy findings suggest that a significant number of oncology patients are experiencing loneliness, most likely as a result of mandate social distancing and isolation procedures. The symptom burden of these patients is extremely high and warrants clinical evaluation and interventions.

ContextA common complaint among oncology patients receiving chemotherapy is altered taste perception.ObjectiveThe purpose of this study was to evaluate for differences in common symptoms and stress levels in patients who reported taste changes.MethodsPatients were receiving chemotherapy for breast, gastrointestinal, gynecological, or lung cancer. Change in the way food tastes (CFT) was assessed using the Memorial Symptom Assessment Scale before the patients' second or third cycle of chemotherapy. Valid and reliable instruments were used to assess for depressive symptoms, state and trait of anxiety, cognitive impairment, diurnal variations in fatigue and energy, sleep disturbance, and pain. Stress was assessed using the Perceived Stress Scale and the Impact of Events Scale-Revised. Multiple logistic regression was used to evaluate for risk factors associated with CFT.ResultsOf the 1329 patients, 49.4% reported CFT. Patients in the CFT group reported higher levels of depression, anxiety, fatigue, and sleep disturbance as well as higher levels of general and disease specific stress. Factors associated with CFT group included being non-White; receiving an antiemetic regimen that contained a neurokinin-1 receptor antagonist with two other antiemetics; having a lower functional status; higher levels of morning fatigue; and reporting higher scores on the hyperarousal subscale of the Impact of Event Scale-Revised.ConclusionsThis study provides new evidence on associations between taste changes and common co-occurring symptoms and stress in oncology patients receiving chemotherapy. Clinicians need to evaluate for taste changes in these patients because this symptom can effect patients' nutritional intake and quality of life.

PurposeNo information is available on cancer patients' knowledge of and experiences with COVID-19. We undertook an evaluation of differences in COVID-19 symptom occurrence rates, COVID-19 testing rates, clinical care activities, knowledge of COVID-19, and use of mitigation procedures between patients who were and were not receiving active cancer treatment.MethodsPatients enrolled were > 18 years of age; had a diagnosis of cancer; and were able to complete the emailed study survey online.ResultsOf the 174 patients who participated, 27.6% (n = 48) were receiving active treatment, 13.6% were unemployed because of COVID-19, 12.2% had been tested for COVID-19, and 0.6% had been hospitalized for COVID-19. Patients who were not on active treatment reported a higher mean number of COVID-19 symptoms (3.1 (± 4.2) versus 1.9 (± 2.6)), and patients who reported a higher number of COVID-19 symptoms were more likely to be tested. Over 55% of the patients were confident that their primary care provider could diagnose COVID-19, and the majority of the patients had high levels of adherence with the use of precautionary measures (e.g., social distancing, use of face coverings).ConclusionThe high level of COVID-19 symptoms and the significant overlap of COVID-19 and cancer-related symptoms pose challenges for clinicians who are assessing and triaging oncology patients for COVID-19 testing. For patients on active treatment, clinicians face challenges with how to assess and manage symptoms that, prior to COVID-19, would be ascribed to acute toxicities associated with cancer treatments or persistent symptoms in cancer survivors.

BackgroundFew qualitative studies of cancer patients' everyday experiences with pain exist within the large body of cancer pain research. Longitudinal qualitative studies are particularly sparse, and no studies have qualitatively described patients' pain experience over time during participation in a self-management intervention.ObjectiveTo longitudinally describe patients' pain experiences during a 10-week pain self-management intervention.MethodsThis qualitative study was embedded in a randomized controlled trial of a psychoeducational pain management intervention. The data consisted of transcribed audio recordings of each intervention session. An emergent, interpretive approach was used in this longitudinal qualitative analysis.ResultsForty-two adult patients were included. The analysis revealed the strikingly dynamic nature of individual patient's pain experiences. Multiple facets of pain contributed to its dynamic nature, including pain in changing locations, co-occurring sources of pain, and varying patterns of pain intensity over time. For individual patients, the cumulative effect of these multiple facets resulted in a phenomenon we termed "complex pain dynamics."ConclusionThe results contribute to knowledge about the dynamic nature of cancer patients' pain experiences over a relatively short period. They suggest the need for a new paradigm for management of pain in cancer patients and raise questions about the interpretation of randomized controlled trial results in the absence of qualitative data.Implications for practiceFrequent assessments and reassessments of pain are needed in cancer patients with the ongoing development of highly individualized self-management strategies. A large repertoire of interventions is needed to effectively manage pain in cancer patients over time.

ContextNo information is available on oncology patients' level of stress and symptom burden during the coronavirus disease 2019 (COVID-19) pandemic.ObjectivesTo evaluate for differences in demographic and clinical characteristics, levels of social isolation and loneliness, and the occurrence and severity of common symptoms between oncology patients with low vs. high levels of COVID-19 and cancer-related stress. In addition, to determine which of these characteristics were associated with membership in the high-stressed group.MethodsPatients were 18 years and older; had a diagnosis of cancer; and were able to complete an online survey.ResultsOf the 187 patients in this study, 31.6% were categorized in the stressed group (Impact of Event Scale-Revised [score of ≥24]). Stressed group's Impact of Event Scale-Revised score exceeds previous benchmarks in oncology patients and equates with probable post-traumatic stress disorder. In this stressed group, patients reported occurrence rates for depression (71.2%), anxiety (78.0%), sleep disturbance (78.0%), evening fatigue (55.9%), cognitive impairment (91.5%), and pain (75.9%). Symptom severity scores equate with clinically meaningful levels for each symptom.ConclusionWe identified alarmingly high rates of stress and an extraordinarily high symptom burden among patients with cancer, exceeding those previously benchmarked in this population and on par with noncancer patients with post-traumatic stress disorder. Given that the COVID-19 pandemic will likely impact cancer care for an indefinite period, clinicians must exhibit increased vigilance in their assessments of patients' level of stress and symptom burden. Moreover, an increase in referrals to appropriate supportive care resources must be prioritized for high-risk patients.

PurposeOlder adults receiving cancer chemotherapy are at increased risk for decrements in physical (PF) and cognitive (CF) function.ObjectivesStudy identified subgroups of patients with distinct PF and CF profiles; risk factors associated with subgroup membership; and impact of subgroup membership on quality of life (QOL).MethodsIn 366 older oncology patients, PF and CF were assessed using the Physical Component Summary (PCS) of the SF-12 and Attentional Function Index, respectively. Latent profile analysis was used to identify subgroups of older patients with distinct PF/CF profiles.ResultsThree distinct PF/CF profiles were identified (i.e., Very Low PF + Moderate CF (15.6%); Low PF + Low CF (39.3%), Normal PF + Normal CF (45.1%)). Compared to the both Normal class, patients in the other two classes had a lower functional status, a worse comorbidity profile, and were less likely to exercise on a regular basis. Compared to the Both Normal class, patients in the Both Low class were less likely to be married/partnered, more likely to live alone, less likely to be employed, and more likely to report depression and back pain. Compared to the other two classes, patients in the Both Low class had a lower annual household income and were receiving chemotherapy with a worse toxicity profile.ConclusionFirst study to use a person-centered analytic approach to identify subgroups of older adults with distinct PF/CF profiles. Fifty-five percent of the older adults had statistically significant and clinically meaningful decrements in both PF AND CF that had negative effects on all aspects of QOL.

PurposeA cancer diagnosis and associated treatments are stressful experiences for most patients. Patients' perceptions of stress and their use of coping strategies may influence fatigue severity. This study extends our previous work describing distinct profiles of morning (i.e., Very Low, Low, High, and Very High) and evening (i.e., Low, Moderate, High, and Very High) fatigue in oncology patients by evaluating for differences in stress and coping strategies among these fatigue classes.MethodsThis longitudinal study evaluated for changes in morning and evening fatigue in oncology patients (n = 1332) over two cycles of chemotherapy (CTX). Patients completed measures of cumulative exposure to stressful life events (SLEs) (i.e., the Life Stressor Checklist-Revised), general stress (i.e., Perceived Stress Scale [PSS]), cancer-specific stress (i.e., Impact of Event Scale-Revised [IES-R]), and coping strategies (i.e., Brief Cope). Differences among the latent classes were evaluated using analyses of variance, Kruskal-Wallis, or chi-square tests.ResultsPatients in both the Very High morning and evening fatigue classes reported higher numbers of and a higher impact from previous SLEs and higher PSS scores than the other fatigue classes. The IES-R scores for the Very High morning fatigue class met the criterion for subsyndromal PTSD. Patients in the Very High evening fatigue class used a higher number of engagement coping strategies compared with the Very High morning fatigue class.ConclusionsOur findings suggest that interventions to reduce stress and enhance coping warrant investigation to decrease fatigue in patients undergoing CTX.

PurposeA breast cancer diagnosis has a substantial economic impact. Study aims were to evaluate for inter-individual differences in cancer's level of interference with employment and identify phenotypic and symptom characteristics associated with higher levels of interference.MethodsPatients (n = 387) were enrolled prior to breast cancer surgery and followed for 12 months. Interference with employment was measured using a 0 (no problem) to 10 (severe problem) numeric rating scale. Hierarchical linear modeling (HLM) was used to evaluate for inter-individual differences in trajectories of employment interference and characteristics associated with employment interference at enrollment and over 12 months.ResultsPatients' mean age was 55.0 (±11.7) years and the majority underwent breast conservation surgery (80.6%). Mean employment interference score was 3.2 (±3.7). Unconditional model for employment interference demonstrated a decreasing linear trend (-.076/month). Younger age, lower income, higher pain intensity, and having an axillary lymph node dissection were associated with higher pre-surgical interference scores. Having a sentinel lymph node biopsy was associated with ongoing employment interference scores. Higher sleep disturbance scores were associated with both initial and ongoing employment interference scores. Receipt of chemotherapy, use of complementary or alternative therapies, and re-excision or mastectomy following surgery were significant time varying covariates.ConclusionThis study is the first to use HLM to describe inter-individual differences in the trajectories of cancer's interference with employment and associated factors prior to and for 12 months following breast cancer surgery. Patients with the identified risk factors warrant ongoing assessments of employment interference and appropriate referrals.