Our Health Library information does not replace the advice of a doctor. Please be advised that this information is made available to assist our patients to learn more about their health. Our providers may not see and/or treat all topics found herein. This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER. During and after treatment for cancer, patients experience an average of 10 to14 co-occurring symptoms.[1,2] Compared with patients with few or no symptoms, patients with multiple concurrent symptoms may experience worse decrements in physical and cognitive function,[3,4,5,6] quality of life,[3,4,5,6] and overall survival.[7] Symptoms that occur together over time may form a cluster. A symptom cluster is two or more concurrent symptoms with the following properties:[1,8] Symptoms in a cluster may be related to each other in multiple ways. They may share a common set of biological, psychological, or social mechanisms, or they may cause or potentiate one another's effects.[8] They may also be due to side effects of another treatment. The management of symptom clusters primarily involves identifying relationships among the symptoms. This approach supports strategies that may address multiple symptoms simultaneously. It also avoids unnecessary interventions that can worsen symptom burden and the patient's quality of life. As advancements in symptom science research are achieved, better therapeutic targets will be identified for improved management of symptom clusters and outcomes. References: To identify cancer-related symptom clusters, investigators ask patients to complete valid, reliable symptom questionnaires.[1] Symptom data can also be obtained directly from clinicians and/or medical records. Symptom data are analyzed to identify symptoms that occur in clusters, using methods such as exploratory factor analysis (EFA).[2,3] The objective of an EFA is to identify groups of symptoms that are correlated with each other. These groups are known as factors or, in the field of symptom cluster research, symptom clusters. Factor analysis is consistent with a biopsychosocial theory [4] that the underlying mechanisms of symptoms are likely shared within symptom clusters. Another method for identifying symptom clusters is through structural equation modeling (SEM).[3] Compared with factor analysis that retrospectively identifies clusters, SEM requires an a priori hypothesis about a common cause of the symptom cluster.[3] One benefit of SEM is that direct and indirect, as well as latent, associations between factors can be identified.[3] This method can help identify risk factors in future patients. Once a symptom cluster has been identified, investigators perform additional analyses to describe patients' experiences with a symptom cluster. A person-centered analytic approach, such as latent class profile analysis, is used to identify and describe subgroups of patients who are similarly burdened by a symptom cluster.[5,6] The symptom cluster burden has multiple dimensions, including the occurrence, frequency, severity, and distress associated with the symptom cluster.[6,7] Determining which patients are at risk for the highest level of symptom cluster burden and associated underlying mechanisms are ongoing areas of research. Common characteristics associated with a higher symptom cluster burden include the following:[1,8,9,10] One limitation in identifying and managing symptom clusters is that symptom assessment tools and analytic approaches may vary across clinical practices. However, the consistency of symptom clusters identified across studies using different instruments supports the fact that core symptoms are being captured and that underlying mechanisms may be associated with symptoms within a cluster. For example, two symptom clusters common to multiple cancer diagnoses and treatment regimens are a sickness behavior syndrome (fatigue, sleep disturbance, lethargy, depression, loss of appetite) [11,12,13] and a psychoneurological symptom cluster (depression, cognitive disturbance, sleep disturbance, fatigue, pain).[14,15] Both of these symptom clusters are associated with underlying inflammatory mechanisms.[11,12,15] Another limitation is that while some symptom clusters appear to be stable over time, [16,17] a patient's symptom experience may vary widely.[7] Specifically, the occurrence of symptoms within a cluster, the level of symptom cluster severity, and the level of distress associated with one or more symptom clusters may shift over time in each individual. Symptom clusters can also persist long after treatment.[7,18] Due to the complexity of symptom clusters, the symptoms within each cluster, and the temporal nature of symptoms/clusters that may shift over time, it is important to continually assess symptoms from diagnosis through the end of life. Retesting symptom clusters through repeated data-driven analyses (e.g., factor analysis,[2,3] SEM,[3]) can help health care professionals to better understand the stability and/or changes in symptom cluster experiences over time. In addition, symptom clusters may differ between individuals who are undergoing active treatment and those who have completed primary therapy. For more information about individual side effects, see the summaries on Supportive and Palliative Care. References: Symptom cluster names are often based on symptoms of the cluster (e.g., psychoneurological[1] and gastrointestinal[2]), although names are not standardized across studies. One frequent unnamed cluster identified across cancer diagnoses includes pain, fatigue, sleep disturbance, and depression.[3] This general symptom cluster has been identified in patients with breast,[4,5] lung,[5,6] gastrointestinal,[5,7] and gynecologic [5,8] cancers. Symptom clusters can also reflect underlying disease (e.g., dyspnea, cough, and fatigue in patients with lung cancer) [9] and/or treatments (e.g., sensory neuropathy symptom cluster, mixed motor-sensory symptom cluster related to chemotherapy-induced peripheral neuropathy).[10] References: Several symptom clusters have been identified across cancer diagnoses and treatments in patients undergoing treatment and throughout survivorship. To date, most studies of symptom clusters in patients undergoing active treatment have analyzed data from patients receiving the same treatment. A limited number of studies suggest the same symptom clusters may occur in groups of patients receiving heterogeneous therapies. A pooled analysis included data from 1,561 patients with advanced cancer in 15 countries. Four symptom clusters were common in patients with myeloma and breast, colorectal, lung, and prostate cancer who were receiving chemotherapy, radiation therapy, analgesics, surgery, and other or no treatments.[1] These clusters included an emotional cluster comprised of feeling tense, worried, irritable, and depressed; a fatigue-pain cluster; a nausea-vomiting cluster; and a cognitive cluster comprised of difficulties with concentration and memory. In another study of 93 Chinese patients with cervical cancer, mood-cognitive, gastrointestinal, sickness behavior, and pain-related symptom clusters were identified in patients receiving chemoradiation therapy, radiation therapy alone, and surgery followed by chemoradiation. Mean symptom severity scores were not significantly different across these three treatment groups.[2] Finally, a longitudinal study of 92 patients with metastatic lung cancer assessed interrelationships between depressive symptoms and a sickness behavior symptom cluster. In this sample, 40.5% of participants were receiving chemotherapy, 35.7% were receiving immunotherapy, and 23.8% were receiving oral targeted therapies. All 12 sickness behavior symptoms were significantly associated with patients' scores on the Patient Health Questionnaire-9 and Hospital Anxiety and Depression Scale depression subscale. Sickness behavior symptom severity was significantly higher in patients receiving chemotherapy than in those receiving oral targeted therapies. However, symptom severity among patients receiving immunotherapy did not differ significantly from symptom severity of the other two groups.[3] In individuals who have completed primary therapy, psychological/cognitive/fatigue clusters are common (e.g., emotional distress, fatigue, cognitive dysfunction;[4] fatigue, difficulty concentrating, drowsiness[5]). In addition, there is evidence for long-term effects in a sickness behavior cluster (e.g., lethargy, sleepiness, depressed mood, hyperalgesia).[6] In a study of 300 patients receiving palliative chemotherapy, one of the symptom clusters identified was fatigue-cognitive, which was associated with decreased functional status and poor quality of life.[5] The authors highlighted that fatigue is often included in other clusters (e.g., fatigue, dyspnea, drowsiness, pain). Fatigue has also been identified in sickness behavior clusters.[6] Because fatigue is prevalent across a number of symptom clusters, it may be helpful to target fatigue to mitigate the effects of symptom clusters across patient populations. Additional research using a person-centered approach is needed to understand the individual experiences of symptom clusters over time. Interventions to mitigate a high symptom burden should be tailored to individual symptom cluster profiles. References: The pathogenesis of symptom clusters has not been clearly established. However, some mechanisms (e.g., chronic inflammation) and interaction effects with patient-specific characteristics (e.g., clinical, environmental, behavioral) are beginning to unfold. Examples of evidence for common pathogenic mechanisms for selected symptom clusters are summarized below. One or more symptoms associated with the sickness behavior syndrome (e.g., fatigue, sleep disturbance, lethargy, depression, loss of appetite) are common in a number of other symptom clusters.[1,2,3] It is a plausible model for understanding the pathogenesis of symptom clusters. The physiological and psychological stress of cancer may be an underlying trigger for the co-occurring symptoms identified in symptom clusters.[4] Central nervous system (CNS) activation of acute psychological stress engages the hypothalamic-pituitary-adrenal axis and sympathetic-adrenal-medullary system to produce increased levels of cortisol. Prolonged stress dampens the homeostatic circadian rhythm of cortisol, causing glucocorticoid resistance, in which immune cells become less sensitive to glucocorticoids.[5] Decreased sensitivity triggers increased levels of glucocorticoids [4,5] as well as epinephrine and norepinephrine.[4] In addition, cellular responses to regain homeostasis, termed allostasis, include secreting catecholamines and cytokines.[5] With chronic stress, allostatic overload occurs with an increase in pro-inflammatory cytokines. In particular, interleukin (IL)-1-beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and others are secreted.[3,4,5] Prolonged secretion of IL-1-beta is associated with sickness behavior symptoms through inducing prostaglandins and activating T and B cells and antibodies.[3,5] In addition, IL-6,[6,7,8] TNF-alpha,[9,10,11], and nuclear-factor kappa B [12]—a transcription factor that induces multiple inflammatory cytokines to enter into circulation—have been associated with high symptom severity. Given the psychological influence of CNS-triggered downstream responses that lead to chronic inflammatory-associated symptoms, individual coping mechanisms and levels of resilience to stress may explain some of the interindividual variability in symptom cluster experiences. Research is just beginning to capture the multiple social determinants of health (e.g., social, structural, environmental, behavioral) that may influence an individual's perception of and response to stress. To best understand the pathogenesis associated with the symptom cluster phenotype, a person-centered approach to research and clinical care is warranted. References: Cancerous tissue and treatment-related side effects are common causes of symptoms within a cluster. Of note, disease and treatments are not always directly related to symptom cluster experiences.[1] In a study of 582 patients receiving treatment for heterogenous types of cancer, the type of cancer diagnosis and treatment received did not predict symptom severity subgroups.[1] This finding suggests that multiple factors likely influence symptom cluster experiences. However, based on known contributors to some symptoms by the type of treatment (e.g., taxane-induced neuropathies [2]), the discussion below highlights symptom clusters identified in patients receiving specific therapies. Chemotherapy A substantial body of research has focused on the symptom experiences of people undergoing chemotherapy. To date, symptom clusters have been identified in patients undergoing chemotherapy for brain,[3] breast,[4,5,6,7,8,9,10,11] gastrointestinal,[12,13] gynecologic,[14,15] hematological,[16,17,18,19] and lung cancers.[20,21] Symptom clusters have also been identified in samples of patients undergoing chemotherapy for heterogenous cancer types.[22,23] In a 2022 systematic review of studies of symptom clusters in patients undergoing chemotherapy, several common symptom clusters were identified across cancer diagnoses. The most common symptom cluster was comprised of psychological symptoms. "Feeling nervous" (or "feeling anxious") and "feeling sad" (or "depressed mood") were the most common symptoms in this cluster. Other common symptoms in this cluster included "feeling irritable," "worrying," and "difficulty concentrating." The second most common symptom cluster involved gastrointestinal symptoms, including nausea and abdominal cramps. Additional symptom clusters identified across diagnoses included the following:[24] Certain symptom clusters are common across a limited number of cancer diagnoses. For example, a systematic review found that a vasomotor-hormonal symptom cluster was identified in studies of patients receiving chemotherapy for breast and gynecologic cancers.[24] Radiation Therapy Symptom clusters have been described in patients receiving radiation therapy (RT) for brain,[25] breast,[26,27] gastrointestinal,[28] head and neck,[29,30,30] and prostate cancers.[31,32] Other studies have found symptoms clusters in patients receiving RT for a number of cancers.[33,34] In a study of 1,224 patients with breast cancer receiving RT, symptoms found to cluster together before, during, and after RT included depression and anxiety, nausea and appetite loss, pain and tiredness, and drowsiness, dyspnea, and tiredness.[26] A study of 100 patients with head and neck cancer in Taiwan who were undergoing postoperative RT identified two symptom clusters that were stable throughout treatment: a head and neck–specific cluster (including pain, dry mouth, appetite, sleep disturbance, fatigue, drowsiness, distress, and sadness) and a gastrointestinal cluster (including nausea, vomiting, numbness, dyspnea, and difficulty with memory).[35] In 843 patients undergoing RT for prostate cancer, seven symptom clusters were identified. Early symptoms, older age, and decreased physical function were associated with the severity of late symptom clusters.[32] In addition, polymorphisms in cytokine genes were associated with symptom clusters in a sample of 157 patients receiving RT for breast and prostate cancer, suggesting that common symptom clusters may be related to inflammatory processes.[36] Polymorphisms in neurotransmitter genes were associated with the severity of sickness behavior, mood-cognitive, and treatment-related symptom clusters, suggesting that mechanisms other than inflammation may also contribute to the development of symptom clusters.[37] Immunotherapy Immunotherapies are a relatively new approach to cancer treatments, and numerous newly developed immunotherapy treatments are in phase I clinical trials. As a result, the scope of symptom clusters in patients receiving these therapies is yet to be understood. References: General Approach The first step in the management of symptom clusters involves an open-ended patient interview to identify symptoms that are bothersome. The next step is to identify the most distressing symptoms with significant negative impact on the patient's quality of life and functioning. A subsequent step is to determine the frequency and severity of the predominant symptoms. This step can be accomplished with a guided interview and objective assessment of individual symptoms using validated questionnaires. For more information, see Fatigue, Depression, and Sleep Disorders. Another important step is to identify the nature of relationships among the symptoms if one exists. This step is critical to minimize unnecessary interventions that might be burdensome for patients already struggling with multiple symptoms and quality-of-life issues. Associations among symptoms in a cluster inform management of symptoms in that cluster. Different ways that symptoms in a cluster may be related to each other include the following: Most symptom management studies test the efficacy of the proposed intervention on a single target symptom as the primary outcome and evaluate secondary impact on a related set of symptoms or on the overall symptom burden.[1,2,3,4] A small number of studies have evaluated the efficacy of certain interventions on multiple co-occurring and related symptoms in symptom clusters. A randomized controlled trial using cognitive behavioral therapy for insomnia (CBT-I) showed improvement in insomnia, fatigue, and depression symptoms.[1,3,4] Another controlled trial found improvement in cognitive, gastrointestinal, and other symptom clusters using a multimodal intervention that included structured exercise, relaxation, and psychosocial support.[5] An important part of managing symptom clusters involves patient and caregiver education. Such education includes discussion of co-occurrence of symptoms and their potential relationship to each other. Patients can also be informed that an intervention targeting a specific symptom may impact other, related symptoms. Another step involves identification of symptoms that may be due to side effects of another intervention. In these cases, addressing the target symptom involves optimizing the triggering intervention or, if possible, considering alternative treatments. If an intervention is deemed necessary, pharmacological and nonpharmacological strategies can be considered (see Table 1). For more information about individual side effects, see the summaries on Supportive and Palliative Care. Pharmacological Interventions Studies investigating pharmacological interventions generally target a primary symptom while evaluating the impact on other, related symptoms as secondary outcomes. Certain pharmacological interventions have shown efficacy in the management of multiple symptoms in separate studies. For example, serotonin-norepinephrine reuptake inhibitors (SNRIs), specifically duloxetine and venlafaxine, are known to treat depression (see the Pharmacological Intervention section in Depression). SNRIs are also effective in the management of chemotherapy-induced peripheral neuropathy (CIPN) (see the Venlafaxine and duloxetine section in Cancer Pain).[6] Venlafaxine has also shown efficacy in the management of hot flashes in breast cancer survivors.[7] These efficacy studies targeting specific symptoms have been conducted in patients with cancer and in general patient populations. When pharmacological interventions are considered, the primary goal is to optimize the medication regimen and minimize side-effect burden. Steps to achieve this goal include the following: Nonpharmacological Interventions Nonpharmacological interventions for the management of cancer-related symptom clusters may include exercise, mindfulness, and psychological therapies. Exercise Exercise has been defined as physical activity that is planned or structured and involves repetitive bodily movements to improve or maintain cardiorespiratory endurance, muscular strength, muscular endurance, flexibility, and body composition. Physical activity has been defined as bodily movements produced by skeletal muscles that result in energy expenditure.[8] Physical activity can include all levels of intensity, including light, moderate, moderate-to-vigorous, and vigorous.[9] The American College of Sports Medicine's published recommendations for exercise in cancer survivors suggest starting slowly and progressing to 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise per week.[10] This aerobic exercise is accompanied by 20 to 30 minutes of strength training across all major muscle groups 2 to 3 times per week and regular stretching daily. Investigators have examined multiple forms of physical activity and their impact on cancer-related symptoms. This activity includes aerobic, anaerobic, muscle-strengthening, bone-strengthening, balance, and flexibility exercises, as well as yoga, tai chi, and qigong. However, most of this research has focused on a primary symptom versus a symptom cluster. A recent consensus statement regarding specific exercise guidelines for cancer survivors identified strong evidence for individual symptom management with exercise for anxiety, depression, and fatigue.[11] (Strong evidence was defined as having five or more randomized controlled trials with samples sizes of more than150 participants.) In addition, strong evidence was identified for better management of lymphedema, physical function, and health-related quality of life with exercise.[11] Of note, moderate evidence for bone health and sleep was identified, while insufficient evidence was found for cardiotoxicity, CIPN, pain, cognitive function, falls, nausea, sexual function, and treatment tolerance.[11] The role of exercise in managing symptom clusters is more limited.[12,13,14,15] One study used a multimodal intervention of structured exercise, relaxation, and psychosocial support to address symptom clusters.[5] It noted improvement in gastrointestinal (nausea, vomiting, stomach pain, loss of appetite, diarrhea), cognitive (diminished concentration, memory problems, fatigue), functional (muscle and joint aches), and mucositis (mouth pain, throat pain, and difficulty swallowing) symptom clusters in the treatment group, but no improvement in an affective (nervousness, anxiety, and stress) symptom cluster, compared with usual care. Mindfulness-based stress reduction (MBSR) Studies investigating mindfulness commonly involve evaluation of its impact on a primary target symptom and on other, related symptoms as secondary outcomes. Studies that examined different approaches to MBSR–British Columbia (MBSR-BC) have found predominantly strong positive impacts on symptoms clusters, including combinations of the following:[16,17,18,19,20,21,22,23,24,25,26] Many of the MBSR interventions involved multiweek programs in which participants were assessed for outcomes at 3-, 6- and 12-month intervals. During this time, survivors participated in mindfulness training and various exercises and were encouraged to continue using these skills on an ongoing basis. Improvement was measured using the following tools and scales: MBSR-BC consists of three components: Many studies have evaluated mindfulness for improvement in anxiety and stress symptoms during cancer treatment. Patients who received MBSR while undergoing chemotherapy were shown to have reduced scores on an "overall suffering score."[16,17,18,21,22,23,24,25] In two of the studies, technology was used to administer the intervention, one online [25] and another via smartphone.[22] These delivery methods provided more opportunities to incorporate mindfulness practices into the treatment of cancer survivors. In addition, some studies showed that the intervention groups had a lower symptom burden, compared with control groups, including more significant remission of both anxiety and depressive symptoms.[20] Measures of health-related quality of life (as demonstrated by the Functional Assessment of Cancer Therapy–Breast) were also significantly higher in the intervention group than in the control group. Fatigue is a common complaint of cancer survivors at all stages, and it contributes to deterioration in many, if not all, psychosocial complaints. Integrating MBSR into cancer care can have many positive outcomes, including reduced fatigue.[17,18,22,26,27] Study participants experienced improvements in other psychosocial areas as well. Compared with control-group participants, those receiving MBSR had a statistically significant reduction in the overall suffering score, improvement in the total Hospital Anxiety and Depression Scale score, and improvement in the total Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being score.[28] In a randomized study of 92 patients, the intervention group experienced positive effects of concurrent MBSR on fatigue and coping while starting adjuvant paclitaxel.[26] While the interventions lasted 1 to 2 months in most cases, results at 6 to 12 months of follow-up showed maintained improvement.[17,18,22,26,27] Another study, of 191 women with documented stress, showed an overall improvement in psychosocial stress and quality-of-life measures after receiving mindfulness-based art therapy (MBAT) versus standard education support groups. Significant improvements were observed immediately after intervention and 6 months later.[29] Patients with self-reported high levels of stress also experienced stress reduction with MBAT, compared with the standard education support groups. Psychological therapies Difficulty with sleep initiation and maintenance often co-occur with anxiety, depression, fatigue, and chronic pain.[30] There are a number of complex interactions with psychological disturbances mediating the relationship between pain and fatigue.[31] With these common symptoms, psychological therapies that target, or are known to create downstream effects on, multiple morbidities help patients address these issues through a single psychotherapeutic approach. Cognitive behavioral therapy (CBT) CBT specifically targets the patient's maladaptive thoughts and behaviors that interfere with quality of life. CBT is a problem-focused form of therapy that encourages patients to take an active role in changing their thoughts and behaviors. This form of therapy can address several different cognitive, behavioral, and health targets. It can be provided in individual, group, or telehealth formats. Mobile apps based on cognitive behavioral principles have been successful in treating common psychological symptoms and psychological symptom clusters.[32] In a multisite randomized controlled trial, 131 patients with cancer were randomly assigned to five sessions of standard CBT, five sessions of profile-tailored CBT, or usual care.[33] Assessments occurred at baseline, 1-month follow-up, and 6-month follow-up. Short- and long-term follow-ups suggested that the patients who received the profile-tailored CBT approach showed significant reductions in levels of pain, pain-associated sleep interference, confusion, bowel patterns, distress, functional status, and mental quality of life, compared with patients in the other two groups. Patients in the standard CBT group showed improvements in the common symptom clusters, compared with patients in the usual care group. In another study, a cohort of 86 patients with mixed cancer diagnoses were randomly assigned to a 2-week, patient-directed intervention using cognitive behavioral principles or usual care.[34] The cognitive-behavioral intervention showed efficacy in treating a pain, fatigue, and sleep-disturbance symptom cluster. For patients experiencing this common symptom cluster acutely or mildly, a self-directed approach may be useful. Acceptance and commitment therapy (ACT) ACT is called a "Third Wave" CBT approach in that there are similarities to CBT, but the goal is to accept emotions and to understand situations that cannot be changed. This approach is considered an emotion-focused form of therapy. It comprises several techniques, including mindfulness and decreasing judgment about one's thoughts and behaviors in any given situation. Studies have shown strong empirical support for ACT's positive benefits for the psychological symptom cluster (depression, anxiety, distress, quality of life) for patients at all stages of cancer. However, few studies have examined its effect on physical and health outcomes.[35] Those studies have shown no significant change in physical markers (pain, fatigue, sleep) after ACT therapy in patients with cancer. While there have been empirical studies of ACT in a number of cultures, countries, and ethnicities, most of the research has focused on female-specific cancers such as breast and ovarian.[36,37,38,39] There is limited empirical research on the applicability of ACT for males with cancer or patients experiencing physical symptoms.[38] Meaning-centered psychotherapy This form of psychotherapy, also called existential psychotherapy or meaning-making psychotherapy, is theoretically rooted in Victor Frankl's book, Man's Search for Meaning.[40] Empirical studies have shown that this approach may be useful for patients experiencing both psychological and common symptom clusters, especially in relation to end-of-life and survivorship concerns.[41] A randomized controlled trial of 253 patients with stage III or IV solid-tumor cancer compared meaning-centered therapy with the active placebo of supportive group therapy. After 8 weekly group sessions, the group receiving meaning-centered therapy had stronger reductions in the psychological symptom clusters, as well as greater increases in spiritual well-being, than the placebo group.[42,43] Meaning-centered psychotherapy has also been tested using an individual therapy approach. A group of 120 patients were randomly assigned to 7 weeks of individual manualized psychotherapy or therapeutic massage. At the end of treatment, patients who received meaning-centered psychotherapy showed improvement in both psychological-cluster symptoms (quality of life, spiritual well-being), as well as physical-cluster symptoms (physical symptom distress, number of physical symptoms).[44] A follow-up study randomly assigned 321 patients with advanced cancer to one of three arms: individual meaning-making psychotherapy, individual supportive psychotherapy, or enhanced usual care. After 8 weeks of treatment, patients receiving meaning-making psychotherapy showed significant improvements in the psychological-symptoms cluster, compared with those receiving enhanced usual care. They also had smaller but significant improvements in the physical-symptoms cluster, compared with those receiving supportive psychotherapy.[45] Specific Evidence-Based Interventions Managing Cancer and Living Meaningfully (CALM) CALM is a brief (2–6 sessions), individual, manualized psychotherapy intervention that is designed to address the psychological symptom cluster in patients with advanced cancer. A randomized controlled trial of 305 patients were divided into CALM (n = 151) or usual care (n = 154) groups. At both the immediate and 6-month follow-up points, patients in the CALM group had fewer depressive symptoms, less end-of-life distress, and greater preparation for the end of life, compared with patients in the usual care group. When CALM outcomes were analyzed among patients with moderate anxiety about death, patients in the CALM group showed significantly greater spiritual well-being and lower levels of anxiety and demoralization at 6 months compared with patients in the usual care group. The brief, individual CALM intervention may be most useful for patients experiencing moderate anxiety about death and the psychological symptom cluster than for those with high or low anxiety about death.[46,47] Cognitive behavioral therapy for insomnia (CBT-I) CBT-I includes techniques such as stimulus control, sleep restriction, and relaxation training to address the cognitive and behavioral components that contribute to disrupted sleep. While CBT-I focuses on sleep, studies have shown that it has other psychological and physical impacts.[48] Studies of CBT-I in patients without cancer have found benefits with pain management, depression, and disability.[49] A 2 x 2 randomized controlled trial of 67 cancer survivors assessed the effects of armodafinil and CBT-I on sleep quality, fatigue, and depression. Symptoms were assessed at three time points: before intervention, immediately after the 7-week intervention, and at the 3-month follow-up. Patients who received CBT-I had significantly improved sleep, fatigue, and depression levels, in addition to reduced hypnotic medication use, at both the post intervention and 3-month follow-up. Patients who received the pharmacological intervention experienced no changes to any of these variables. Path analysis showed that improvement in depressive symptoms was mediated by insomnia severity, suggesting that treatment of sleep disruptions with CBT-I can have a clinically meaningful effect on depressive symptoms.[3] Studies of CBT-I in patients without cancer have found additional benefits for pain management, depression, and disability.[49] There is extremely limited data on the effect of CBT-I on pain outcomes in patients with cancer. When patients with cancer are treated at the acute stage of insomnia, minimal and digital forms of CBT-I have also been found to be useful in randomized controlled trials. Minimal forms include psychoeducation booklets and three phone consultations with a sleep psychologist.[50] Digital forms include self-directed apps via computer or smartphone.[51] These studies have found an impact of CBT-I on sleep measures, as well as psychological-cluster symptoms (depression, anxiety, distress). Psilocybin-assisted psychotherapy A potential treatment to address the psychological and common symptom clusters is psilocybin-assisted psychotherapy. While more research is needed before it becomes an evidence-based practice, promising early research results have been disseminated widely on a number of news and blog sites, increasing patient interest in this approach to therapy. In a double-blind randomized controlled trial, 29 patients with advanced cancer and related anxiety and depression received 7 weeks of psychotherapy and a single dose of either psilocybin or niacin. Patients who received the psilocybin plus psychotherapy showed significant reductions in the severity of symptoms in the psychological symptom cluster.[52] A follow-up study of patients who were still alive (n = 15) showed that these improvements were maintained for 3.2 to 4.5 years after the original study.[53] This emerging treatment continues to develop with wider groups of cancer patients and long-term assessments of multisymptom clusters. References: The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above. Editorial changes were made to this summary. This is a new summary. This summary is written and maintained by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages. Purpose of This Summary This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the identification and management of symptom clusters. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions. Reviewers and Updates This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH). Board members review recently published articles each month to determine whether an article should: Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary. The lead reviewers for Symptom Clusters in Cancer are: Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries. Levels of Evidence Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Permission to Use This Summary PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]." The preferred citation for this PDQ summary is: PDQ® Supportive and Palliative Care Editorial Board. PDQ Symptom Clusters in Cancer. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/cancer-symptom-clusters-hp-pdq. Accessed <MM/DD/YYYY>. Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images. Disclaimer The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page. Contact Us More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us. Last Revised: 2024-07-11 This information does not replace the advice of a doctor. Ignite Healthwise, LLC disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use and Privacy Policy. Learn how we develop our content. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Ignite Healthwise, LLC.Topic Contents
Symptom Clusters in Cancer (PDQ®): Supportive care - Health Professional Information [NCI]
Overview
Identification of Symptom Clusters: Methods and Limitations
Predictors and Outcomes of Select Symptom Clusters
Symptom Clusters Common Across Heterogeneous Treatments
Pathogenesis of Symptom Clusters
Symptom Clusters by Treatment Modality
Management of Cancer-Related Symptom Clusters
Symptoms SNRIsa Exercise E+R Mindfulness CBT ACT MCP PAP MBSR-BC MBAT CBT CBT-I ACT = acceptance and commitment therapy; CBT = cognitive behavioral therapy; CBT-I = cognitive behavioral therapy–insomnia; CIPN = chemotherapy-induced peripheral neuropathy; E+R = exercise + relaxation; MBAT = mindfulness-based art therapy; MBSR-BC = mindfulness-based stress reduction–British Columbia; MCP = meaning-centered psychotherapy; PAP = psilocybin-assisted psychotherapy; SNRIs = serotonin-norepinephrine reuptake inhibitors. a Duloxetine and venlafaxine. Depression X X X X X X X Pain X CIPN X Lymphedema X Anxiety X X X X X Hot flashes X Fatigue X X X X Low energy X Sleep disturbance X X X Bowel dysfunction X Perceived stress/distress X X X X Physical function X X Psychological/psychosocial function X X X Spiritual well-being X Quality of life X X X X Symptom Clusters Gastrointestinal (nausea, vomiting, stomach pain, loss of appetite, diarrhea) X Cognitive (decreased concentration, memory problems, fatigue) X Functional (muscle aches, joint aches) X Mucositis; mouth pain (throat pain, difficulty swallowing) X Latest Updates to This Summary (07 / 11 / 2024)
About This PDQ Summary
Our Health Library information does not replace the advice of a doctor. Please be advised that this information is made available to assist our patients to learn more about their health. Our providers may not see and/or treat all topics found herein. This information does not replace the advice of a doctor. Ignite Healthwise, LLC disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use and Privacy Policy. Learn how we develop our content. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Ignite Healthwise, LLC.Symptom Clusters in Cancer (PDQ®): Supportive care - Health Professional Information [NCI]