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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.

PurposeRelatively few studies have evaluated for symptom clusters across multiple dimensions. It is unknown whether the symptom dimension used to create symptom clusters influences the number and types of clusters that are identified. Study purposes were to describe ratings of occurrence, severity, and distress for 38 symptoms in a heterogeneous sample of oncology patients (n = 1329) undergoing chemotherapy; identify and compare the number and types of symptom clusters based on three dimensions (i.e., occurrence, severity, and distress); and identify common and distinct clusters.MethodsA modified version of the Memorial Symptom Assessment Scale was used to assess the occurrence, severity, and distress ratings of 38 symptoms in the week prior to patients' next cycle of chemotherapy. Symptom clusters for each dimension were identified using exploratory factor analysis.ResultsPatients reported an average of 13.9 (±7.2) concurrent symptoms. Lack of energy was both the most common and severe symptom while "I don't look like myself" was the most distressing. Psychological, gastrointestinal, weight gain, respiratory, and hormonal clusters were identified across all three dimensions. Findings suggest that psychological, gastrointestinal, and weight gain clusters are common while respiratory and hormonal clusters are distinct.ConclusionsPsychological, gastrointestinal, weight gain, hormonal, and respiratory clusters are stable across occurrence, severity, and distress in oncology patients receiving chemotherapy. Given the stability of these clusters and the consistency of the symptoms across dimensions, the use of a single dimension to identify these clusters may be sufficient. However, comprehensive and disease-specific inventories need to be used to identify distinct clusters.

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.

PURPOSE: A breast cancer diagnosis has a substantial economic impact. Study aims were to evaluate for inter-individual differences in cancers level of interference with employment and identify phenotypic and symptom characteristics associated with higher levels of interference. METHODS: Patients (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. RESULTS: Patients 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. CONCLUSION: This study is the first to use HLM to describe inter-individual differences in the trajectories of cancers 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.

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.

PurposeBetween 19 and 58% of oncology patients experience chemotherapy-induced nausea (CIN). In a sample of outpatients with breast, gastrointestinal (GI), gynecological, and lung cancer, the study purposes were to evaluate for inter-individual differences in the severity of CIN over two cycles of chemotherapy (CTX) and to determine which demographic and clinical characteristics and GI symptoms were associated with higher initial levels as well as with the trajectories of CIN severity.MethodsPatients completed study questionnaires at six time points over two cycles of CTX. These questionnaires provided information on demographic and clinical characteristics, as well as the occurrence of twelve GI symptoms. Hierarchical linear modeling based on full maximum likelihood estimation was performed.ResultsOf the 1251 patients, 47.2% reported CIN. Across two cycles of CTX, lower functional status scores and higher levels of comorbidity were associated with higher initial levels of CIN. Younger age and emetogenicity of the CTX regimen were associated with higher initial levels as well as worse trajectories of CIN. The occurrence of five GI symptoms (i.e., vomiting, lack of appetite, constipation, feeling bloated, and difficulty swallowing) was associated with higher initial levels of CIN. The occurrence of mouth sores was associated with higher initial levels as well as with worst trajectories of CIN.ConclusionsThis study is the first to identify distinct demographic, clinical, and GI symptom characteristics associated with CIN severity. These findings suggest that the etiology of CIN is complex and may warrant interventions beyond standard antiemetics.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individuals specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.

PurposeWhile older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors.MethodsCancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory, and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (

PurposeFatigue is the most common symptom associated with cancer and its treatment. Investigation of molecular mechanisms associated with fatigue in oncology patients may identify new therapeutic targets. The objectives of this study were to evaluate the relationships between gene expression and perturbations in biological pathways and evening fatigue severity in oncology patients who received chemotherapy (CTX).MethodsThe Lee Fatigue Scale (LFS) and latent class analysis were used to identify evening fatigue phenotypes. We measured 47,214 ribonucleic acid transcripts from whole blood collected prior to a cycle of CTX. Perturbations in biological pathways associated with differential gene expression were identified from public data sets (i.e., Kyoto Encyclopedia Gene and Genomes, BioCarta).ResultsPatients were classified into Moderate (n = 65, mean LFS score 3.1) or Very High (n = 195, mean LFS score 6.4) evening fatigue groups. Compared to patients with Moderate fatigue, patients with Very High fatigue exhibited differential expression of 29 genes. A number of the perturbed pathways identified validated prior mechanistic hypotheses for fatigue, including alterations in immune function, inflammation, neurotransmission, energy metabolism, and circadian rhythms. Based on our findings, energy metabolism was further divided into alterations in carbohydrate metabolism and skeletal muscle energy. Alterations in renal function-related pathways were identified as a potential new mechanism.ConclusionsThis study identified differential gene expression and perturbed biological pathways that provide new insights into the multiple and likely inter-related mechanisms associated with evening fatigue in oncology patients.

PurposePurposes of this study were to identify subgroups of patients with distinct trajectories for morning and evening fatigue, evaluate for differences in demographic and clinical characteristics among these subgroups, and compare and contrast the predictors of subgroup membership for morning and evening fatigue.MethodsOutpatients with breast, gastrointestinal, gynecological, or lung cancer (n = 582) completed questionnaires, a total of six times over two cycles of chemotherapy (CTX). Morning and evening fatigue severity were evaluated using the Lee Fatigue Scale. Latent profile analysis (LPA) was used to identify distinct subgroups.ResultsThree latent classes were identified for morning fatigue (i.e., low (31.8 %), high (51.4 %), and very high (16.8 %)) and for evening fatigue (i.e., moderate (20.0 %), high (21.8 %), and very high (58.2 %)). Most of the disease and treatment characteristics did not distinguish among the morning and evening fatigue classes. Compared to the low class, patients in the high and very high morning fatigue classes were younger, had a lower functional status, and higher level of comorbidity. Compared to the moderate class, patients in the very high evening fatigue class were younger, more likely to be female, had child care responsibilities, had a lower functional status, and a higher level of comorbidity.ConclusionLPA allows for the identification of risk factors for more severe fatigue. Since an overlap was not observed across the morning and evening fatigue classes and unique predictors for morning and evening fatigue were identified, these findings suggest that morning and evening fatigue may have distinct underlying mechanisms.

PurposeUnderstanding the etiology of cancer-related fatigue (CRF) is critical to identify targets to develop therapies to reduce CRF burden. The goal of this systematic review was to expand on the initial work by the National Cancer Institute CRF Working Group to understand the state of the science related to the biology of CRF and, specifically, to evaluate studies that examined the relationships between biomarkers and CRF and to develop an etiologic model of CRF to guide researchers on pathways to explore or therapeutic targets to investigate.MethodsThis review was completed by the Multinational Association of Supportive Care in Cancer Fatigue Study Group-Biomarker Working Group. The initial search used three terms (biomarkers, fatigue, cancer), which yielded 11,129 articles. After removing duplicates, 9145 articles remained. Titles were assessed for the keywords "cancer" and "fatigue" resulting in 3811 articles. Articles published before 2010 and those with samples