COVID-19 pandemic stress and cancer symptom burden.

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.

Epigenetic Regulation of Inflammatory Mechanisms and a Psychological Symptom Cluster in Patients Receiving Chemotherapy.

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.

Gastrointestinal Symptom Cluster is Associated With Epigenetic Regulation of Lymphotoxin Beta in Oncology Patients Receiving Chemotherapy.

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.

Symptom clusters in outpatients with cancer using different dimensions of the symptom experience.

PURPOSE: Relatively 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. METHODS: A 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. RESULTS: Patients 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. CONCLUSIONS: Psychological, 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.

Advances in Conceptual and Methodological Issues in Symptom Cluster Research: A 20-Year Perspective.

Two conceptual approaches are used to evaluate symptom clusters: "clustering" symptoms (ie, variable-centered analytic approach) and "clustering" patients (ie, person-centered analytic approach). However, these methods are not used consistently and conceptual clarity is needed. Given the emergence of novel methods to evaluate symptom clusters, a review of the conceptual basis for older and newer analytic methods is warranted. Therefore, this article will review the conceptual basis for symptom cluster research; compare and contrast the conceptual basis for using variable-centered versus patient-centered analytic approaches in symptom cluster research; review their strengths and weaknesses; and compare their applications in symptom cluster research.

Symptom clusters in patients receiving chemotherapy: A systematic review.

BACKGROUND AND PURPOSE: Since 2001, symptom cluster research has grown considerably. However, because multiple methodological considerations remain, ongoing synthesis of the literature is needed to identify gaps in this area of symptom science. This systematic review evaluated the progress in symptom clusters research in adults receiving primary or adjuvant chemotherapy since 2016. METHODS: Eligible studies were published in English between 1 January 2017 and 17 May 2021; evaluated for and identified symptom clusters 'de novo;' and included only adults being treated with primary or adjuvant chemotherapy. Studies were excluded if patients had advanced cancer or were receiving palliative chemotherapy; symptoms were measured after treatment; symptom clusters were pre-specified or a patient-centred analytic approach was used. For each study, symptom instrument(s); statistical methods and symptom dimension(s) used to create the clusters; whether symptoms were allowed to load on more than one factor; method used to assess for stability of symptom clusters and associations with secondary outcomes and biomarkers were extracted. RESULTS: Twenty-three studies were included. Memorial Symptom Assessment Scale was the most common instrument and exploratory factor analysis was the most common statistical method used to identify symptom clusters. Psychological, gastrointestinal, and nutritional clusters were the most commonly identified clusters. Only the psychological cluster remained relatively stable over time. Only five studies evaluated for secondary outcomes. DISCUSSION: While symptom cluster research has evolved, clear criteria to evaluate the stability of symptom clusters and standardised nomenclature for naming clusters are needed. Additional research is needed to evaluate the biological mechanism(s) for symptom clusters. PROSPERO REGISTRATION NUMBER: CRD42021240216.

Cancer-related cognitive impairment is associated with perturbations in inflammatory pathways.

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 <5 and 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 <5 and 50.8% had an AFI score of >7.5. Of the 158 patients in Sample 2, 50.6% had an AFI score of <5 and 49.4% 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.

Multi-Staged Data-Integrated Multi-Omics Analysis for Symptom Science Research.

The incorporation of omics approaches into symptom science research can provide researchers with information about the molecular mechanisms that underlie symptoms. Most of the omics analyses in symptom science have used a single omics approach. Therefore, these analyses are limited by the information contained within a specific omics domain (e.g., genomics and inherited variations, transcriptomics and gene function). A multi-staged data-integrated multi-omics (MS-DIMO) analysis integrates multiple types of omics data in a single study. With this integration, a MS-DIMO analysis can provide a more comprehensive picture of the complex biological mechanisms that underlie symptoms. The results of a MS-DIMO analysis can be used to refine mechanistic hypotheses and/or discover therapeutic targets for specific symptoms. The purposes of this paper are to: (1) describe a MS-DIMO analysis using "Symptom X" as an example; (2) discuss a number of challenges associated with specific omics analyses and how a MS-DIMO analysis can address them; (3) describe the various orders of omics data that can be used in a MS-DIMO analysis; (4) describe omics analysis tools; and (5) review case exemplars of MS-DIMO analyses in symptom science. This paper provides information on how a MS-DIMO analysis can strengthen symptom science research through the prioritization of functional genes and biological processes associated with a specific symptom.

Stability of Symptom Clusters in Patients With Breast Cancer Receiving Chemotherapy.

CONTEXT: Patients with breast cancer who undergo chemotherapy (CTX) experience between 10 and 32 concurrent symptoms. An evaluation of how these symptoms cluster together and how these symptom clusters change over time may provide insights into how to treat these multiple co-occurring symptoms. OBJECTIVES: The purposes of this study were to determine the occurrence rates and severity ratings for 38 common symptoms, evaluate for differences in the number and types of symptom clusters, and evaluate for changes over time in these symptom clusters (i.e., before CTX, the week after CTX, and two weeks after CTX). METHODS: At each of the assessments, a modified version of the Memorial Symptom Assessment Scale was used to assess the occurrence and severity of the 38 symptoms. Exploratory factor analyses were used to extract the symptom clusters. RESULTS: Although across the two symptom dimensions (i.e., occurrence and severity) and the three assessments, eight distinct symptom clusters were identified, only five were relatively stable across both dimensions and across time (i.e., psychological, hormonal, nutritional, gastrointestinal, and epithelial). Two of the additional clusters varied by time but not by symptom dimension (i.e., sickness behavior and weight change). The CTX neuropathy cluster was identified only at the assessment performed in the week after CTX. CONCLUSION: These findings provide insights into the most common symptom clusters in patients undergoing CTX for breast cancer. In addition, the most common symptoms within each cluster appear to be relatively stable across the two dimensions, as well as across time.

Differences in symptom clusters identified using symptom occurrence rates versus severity ratings in patients with breast cancer undergoing chemotherapy.

PURPOSE: One of the unanswered questions in symptom clusters research is whether the number and types of symptom clusters vary based on the dimension of the symptom experience used to create the clusters. Given that patients with breast cancer receiving chemotherapy (CTX), report between 10 and 32 concurrent symptoms and studies of symptom clusters in these patients are limited, the purpose of this study, in breast cancer patients undergoing CTX (n = 515), was to identify whether the number and types of symptom clusters differed based on whether symptom occurrence rates or symptom severity ratings were used to create the clusters. METHODS: A modified version of the Memorial Symptom Assessment Scale was used to assess for the occurrence and severity of 38 symptoms, one week after the administration of CTX. Exploratory factor analysis was used to extract the symptom clusters. RESULTS: Both the number and types of symptom clusters were similar using symptom occurrence rates or symptom severity ratings. Five symptom clusters were identified using symptom occurrence rates (i.e., psychological, hormonal, nutritional, gastrointestinal, epithelial). Six symptom clusters (i.e., psychological, hormonal, nutritional, gastrointestinal, epithelial, chemotherapy neuropathy) were identified using symptom severity ratings. Across the two dimensions, the specific symptoms within each of the symptom clusters were similar. CONCLUSIONS: Identification of symptom clusters in patients with breast cancer may be useful in guiding symptom management interventions. Future studies are warranted to determine if symptom clusters remain stable over a cycle of CTX in patients with breast cancer.

Potassium Channel Candidate Genes Predict the Development of Secondary Lymphedema Following Breast Cancer Surgery.

BACKGROUND: Potassium (K) channels play an important role in lymph pump activity, lymph formation, lymph transport, and the functions of lymph nodes. No studies have examined the relationship between K channel candidate genes and the development of secondary lymphedema (LE). OBJECTIVE: The study purpose was to evaluate for differences in genotypic characteristics in women who did (n = 155) or did not (n = 387) develop upper extremity LE following breast cancer treatment based on an analysis of single-nucleotide polymorphisms (SNPs) and haplotypes in 10 K channel genes. METHODS: Upper extremity LE was diagnosed using bioimpedance resistance ratios. Logistic regression analyses were used to identify those SNPs and haplotypes that were associated with LE while controlling for relevant demographic, clinical, and genomic characteristics. RESULTS: Patients with LE had a higher body mass index, had a higher number of lymph nodes removed, had more advanced disease, received adjuvant chemotherapy, received radiation therapy, and were less likely to have undergone a sentinel lymph node biopsy. One SNP in a voltage-gated K channel gene (KCNA1 rs4766311), four in two inward-rectifying K channel genes (KCNJ3 rs1037091 and KCNJ6 rs2211845, rs991985, rs2836019), and one in a two-pore K channel gene (KCNK3 rs1662988) were associated with LE. DISCUSSION: These preliminary findings suggest that K channel genes play a role in the development of secondary LE.

Epigenetic regulation and measurement of epigenetic changes.

Epigenetic mechanisms provide an adaptive layer of control in the regulation of gene expression that enables an organism to adjust to a changing environment. Epigenetic regulation increases the functional complexity of deoxyribonucleic acid (DNA) by altering chromatin structure, nuclear organization, and transcript stability. These changes may additively or synergistically influence gene expression and result in long-term molecular and functional consequences independent of the DNA sequence that may ultimately define an individual's phenotype. This article (1) describes histone modification, DNA methylation, and expression of small noncoding RNA species; (2) reviews the most common methods used to measure these epigenetic changes; and (3) presents factors that need to be considered when choosing a specific tissue to evaluate for epigenetic changes.

A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients.

PURPOSE: Evidence for chemotherapy-induced cognitive impairment remains inconclusive. This study was designed to determine the trajectory of cognitive function over time in women with breast cancer, who received doxorubicin and cyclophosphamide (AC) alone or followed by a taxane. Associations between changes in cognitive function and potential covariates including anxiety, depression, fatigue, hemoglobin level, menopausal status, and perception of cognitive function were evaluated. METHODS: The Repeatable Battery for the Assessment of Neuropsychological Status, Stroop Test, and Grooved Pegboard were used to assess cognitive function in a group of 71 women prior to chemotherapy, a week after completing the last cycle of AC, as well as 1 week and 6 months after the completion of all chemotherapy. RESULTS: Cognitive impairment was found in 23% of women prior to chemotherapy. Hierarchical linear modeling showed significant decreases after receiving chemotherapy followed by improvements 6 months after the completion of chemotherapy in the cognitive domains of visuospatial skill (p < 0.001), attention (p = 0.022), delayed memory (p = 0.006), and motor function (p = 0.043). In contrast, immediate memory, language, and executive function scores did not change over time. CONCLUSION: These results suggest that having a breast cancer diagnosis may be associated with cognitive impairment. While chemotherapy may have a negative impact on cognitive function, chemotherapy-related impairments appear to be more acute than chronic side effects of therapy. Further studies are needed to provide insight into the clinical significance and potential mechanisms of cancer and treatment-related cognitive impairments.

Risk factors and symptoms associated with pain in HIV-infected adults.

Studies suggest that people living with HIV (PLWH) experience many unrelieved symptoms. The purpose of this study was to estimate the occurrence of pain in adult PLWH and to determine whether participants with pain differed from those without pain on selected demographic factors, clinical characteristics, symptoms of fatigue, sleep disturbance, anxiety, or depression. The authors conducted a descriptive, comparative, and correlational study of 317 PLWH seen at academic and community clinics in San Francisco. Participants completed a demographic questionnaire, the Memorial Symptom Assessment Scale, the Fatigue Severity Scale, the General Sleep Disturbance Scale, the Profile of Moods State Tension-Anxiety subscale, and the Center for Epidemiological Studies-Depression Scale. Clinical characteristics (i.e., disease and treatment information) were obtained by self-report. A single item on pain from the Memorial Symptom Assessment Scale was used to classify participants into those with and without pain. Pain was highly prevalent (55%) and was associated with immune status (CD4+ T-cell count), race, and sleep disturbance, but not with age, gender, or symptoms of fatigue, depression, or anxiety.

Preliminary results of a longitudinal study of changes in cognitive function in breast cancer patients undergoing chemotherapy with doxorubicin and cyclophosphamide.

OBJECTIVES: Recent studies suggest that standard dose chemotherapy for breast cancer may cross the blood-brain barrier. However, the evidence for chemotherapy-induced cognitive impairments in breast cancer patients is inconsistent. The purposes of this study in a sample of newly diagnosed patients with breast cancer were to (1) evaluate cognitive function prior to the administration of chemotherapy; (2) assess changes in cognitive function over time; and (3) evaluate potential relationships between cognitive function and anxiety, depression, fatigue, hemoglobin level, menopausal status, and perception of cognitive function. METHODS: Thirty women with breast cancer completed neuropsychological testing before the initiation of chemotherapy and after four cycles of doxorubicin and cyclophosphamide. Descriptive statistics were used to summarize sample characteristics, and paired t-tests were carried out to evaluate for changes in neuropsychological test scores prior to and following completion of chemotherapy. Linear mixed model analyses were used to determine whether significant changes in neuropsychological test scores remained after controlling for anxiety, depression, fatigue, hemoglobin level, menopausal status, and perceived cognitive function. RESULTS: Significant decreases in visuospatial skill (p<0.001) and total cognitive scores (p=0.001) were found following chemotherapy. In addition, a significant improvement was found in executive function (p=0.014). Of note, these changes remained significant even after controlling for anxiety, depression, fatigue, hemoglobin level, menopausal status, and perceived cognitive function. CONCLUSIONS: Data from this study supported the hypothesis that chemotherapy may have a negative impact on select domains of cognitive function.

Prevalence, severity, and impact of symptoms on female family caregivers of patients at the initiation of radiation therapy for prostate cancer.

PURPOSE: In a sample of family caregivers (FCs) of patients with prostate cancer who were to begin radiation therapy (RT), the purposes were to determine the prevalence and severity of depression, anxiety, pain, sleep disturbance, and fatigue; determine the relationships among these symptoms and between these symptoms and functional status and quality of life (QOL); evaluate for differences in functional status and QOL between FCs with low and high levels of these symptoms; and determine which factors predicted FCs' functional status and QOL. PATIENTS AND METHODS: FCs were recruited before patients initiated RT and completed self-report questionnaires that evaluated demographic characteristics, symptoms, functional status, and QOL. RESULTS: Sixty female FCs participated in the study. On the basis of established cut point scores for each symptom questionnaire, 12.2% of the FCs had clinically meaningful levels of depression, 40.7% anxiety, 15.0% pain, 36.7% sleep disturbance, 33.3% morning fatigue, and 30.0% evening fatigue. FCs who were older and who had lower levels of state anxiety and higher levels of depression, morning fatigue, and pain reported significantly poorer functional status (R(2) = 38.7%). FCs who were younger, had more years of education, were working, and who had higher levels of depression, morning fatigue, sleep disturbance, and lower levels of evening fatigue reported significantly lower QOL scores (R(2) = 70.1%). CONCLUSION: A high percentage of FCs experienced clinically meaningful levels of a variety of symptoms. These symptoms have a negative impact on the FCs' functional status and QOL.

A meta-analysis of the sensitivity of various neuropsychological tests used to detect chemotherapy-induced cognitive impairment in patients with breast cancer.

PURPOSE/OBJECTIVES: To identify which neuropsychological tests have been used to evaluate chemotherapy-induced impairment in various domains of cognitive function in patients with breast cancer and to determine the sensitivity of each of the tests through estimation of effect size. DATA SOURCES: Original studies published from 1966-June 2006. DATA SYNTHESIS: Although an array of neuropsychological tests are available to measure the various domains of cognitive function, information is lacking regarding the sensitivity and specificity of the tests to detect changes in cognitive function from chemotherapy. CONCLUSIONS: This meta-analysis provides initial data on the sensitivity of some neuropsychological tests to determine chemotherapy-induced changes in cognitive function in patients with breast cancer. IMPLICATIONS FOR NURSING: The identification of sensitive neuro-psychological tests is crucial to further understanding of chemotherapy-induced cognitive impairments.

Hospice care in nursing homes: does it contribute to higher quality pain management?

PURPOSE: The purpose of this study was to investigate pain management among 42 hospice and 65 non-hospice residents in two proprietary nursing homes. DESIGN AND METHODS: In this prospective, anthropological, quantitative, and qualitative study, we used participant observation, event analysis, and chart review to obtain data. The Medication Quantification Scale was used in order to account for the prescription and administration of all analgesic medications. RESULTS: Although 72% of residents experienced pain, we found no statistically significant differences in the proportion of hospice versus non-hospice residents (a) who had been prescribed opioids and co-analgesics, and (b) whose medication was administered around the clock or as needed. Limited physician availability, lack of pharmacologic knowledge, and limitations of nursing staff hindered pain management of both groups of residents. IMPLICATIONS: Although hospice care is of some benefit, pain management and high-quality end-of-life care is dependent upon the context in which it is provided. Given that between 1991 and 2001 Medicare expenditures for nursing home-based hospice care increased from dollar 8.6 million to dollar 21.8 million, the effectiveness of hospice-care programs in nursing homes warrants further study.

Pain management autobiographies and reluctance to use opioids for cancer pain management.

Although pain management education results in improved pain control for some patients, it does not work for all patients because some patients remain reluctant or unwilling to use prescribed analgesics to their optimal effect. In a randomized clinical trial that tested the effectiveness of the PRO-SELF Pain Control Program, 11 patients declined to increase their analgesic use despite moderate to severe pain. These patients were selected for a qualitative analysis of their audiotaped discussions about pain management with their intervention nurses. This analysis revealed that these patients often spontaneously provided detailed explanations about why they were reluctant or unwilling to take analgesics in general or opioids in particular. We termed these explanatory accounts pain management autobiographies because of their narrative character and multilayered, richly detailed quality. Pain management autobiographies included stories about (1) previous experience with chronic pain management, including stigmatizing interactions with clinicians and family members; (2) bad experiences with cancer pain management, including severe constipation; and 3) strongly held conventions about medication use, including the belief that all medications are "toxins" that should be avoided. The study findings suggest that a small subset of patients with cancer pain may need interventions such as individual or family counseling or alternative pain management strategies to augment education about opioids.