Research on symptom clusters is regarded as cutting-edge science and a new frontier in the field of cancer symptom management.1 Patients with cancer often have multiple symptoms simultaneously that may or may not relate to each other.1,2 Based on this point, research focusing on single symptoms may not be adequate to guide clinical practice.3,4 In 2001, Dodd et al5 further defined a symptom cluster as 3 or more concurrent symptoms related to each other. This definition was later revised by pointing out only 2 or more related symptoms that occur together and form a stable group and are relatively independent of other clusters can be considered a symptom cluster.3 Since then, great efforts have been put into examining symptom clusters in patients with cancer.
The concept of multiple symptoms emphasizes the occurrence of a number of symptoms that are not necessarily interrelated. In contrast, symptoms within a cluster usually have similarity in their origin, etiology, and outlook and therefore have the potential to be treated simultaneously by a shared intervention to improve the use of healthcare human resource and patients’ time.6
Managing a symptom cluster as a whole instead of single symptoms could be more efficient and effective.7,8 A recent review on managing symptom clusters identified several interventions, pharmacological and nonpharmacological, being tested on patients with cancer.9 Nonpharmacological interventions such as psychoeducational intervention (PEI) were most likely to generate positive patient outcomes.8 However, caution is warranted with this finding because some included studies examined multiple discrete symptoms that may not be directly generalized to symptom clusters.
Psychoeducational intervention is well established as an adjunctive treatment for cancer.10 It refers to “therapeutic approaches that involve information giving and receiving, discussion of concerns, problem solving, coping skills training, expression of emotion, and social support.”11(p73) According to Barsevick et al,11 PEI can be further classified into 5 categories: counseling/psychotherapy, behavior therapy, education/information, social support, and other (any usual therapies of a psychosocial nature not mentioned in previous categories such as music therapy). Psychoeducational intervention intends to prepare patients with adequate knowledge and skills to perform self-care practices and to have the confidence and motivation to initiate and sustain self-care efforts.12,13
Psychoeducational intervention has been broadly used in cancer care to improve psychological and physiological outcomes, thus enhancing patients’ quality of life (QOL).14 Given et al15 emphasized PEI’s “value-added” role in cancer symptom management, over and above pharmacological treatments. Furthermore, in Williams’ review,16 PEI was highlighted as showing some efficacy in decreasing multiple concurrent symptoms. Symptom clusters were not examined in that review because no studies had been conducted on treating symptom clusters at that time. Whether PEI is an effective approach to managing symptom clusters is unknown and is examined in the present review.
The outcomes selected for this review were derived from the updated Theory of Unpleasant Symptom (TOUS).17 The TOUS has 3 major reciprocal components: influencing factors, symptoms, and functional performance. The first component (influencing factors) influences the nature of the symptom experience, which in turn impacts functional performance. This review is focused on the symptom experience and functional performance. Symptoms are the central concept and can occur in isolation or, more often, in combination with other symptoms. Although the term “symptom cluster” is not explicitly used in the TOUS, the theory sheds light on the study of symptom clusters and hence was adopted for this review. According to the theory, each symptom has 4 dimensions: intensity, timing, distress, and quality, which are assumed to be separate but related. Functional performance is the consequence of the symptom experience and includes physical functioning, activities of daily living, social activities, role performance, and cognitive performance. Quality of life is also examined in this review because developers of the TOUS recently recognized QOL as another important outcome of symptom experience, and they are exploring its position in the theory.18
The purpose of the present systematic review was to evaluate the effectiveness of PEI on managing symptom clusters in patients with cancer and the efficacy of PEI on functional performance and QOL. We posed the following research questions:
- What is the effectiveness of PEI for improving symptom clusters in patients with cancer?
- What is the effectiveness of PEI on functional performance and QOL under the circumstance of examining symptom clusters?
- What is the effectiveness of various types, interveners, delivery formats, provision time frames, and duration of PEI on managing symptom clusters?
TYPES OF STUDIES
Studies included in this review were limited to randomized controlled trials (RCTs) in order to provide high-quality evidence.19 Eligible articles were written in English and published since the year 2001, when the concept of symptom cluster was brought into cancer care. Articles with their full texts being unavailable were excluded.
TYPES OF PARTICIPANTS
Participants were adult patients who received a diagnosis of cancer.
TYPES OF INTERVENTIONS
Psychoeducational intervention was delivered in 1 type or in a combination of the following intervention categories: counseling/psychotherapy, behavior therapy, education/information, social support, and other (any usual therapies of a psychosocial nature not mentioned in previous categories such as music therapy).11
TYPES OF OUTCOME MEASURES
The primary outcomes were symptom clusters, expressed in terms of intensity, timing, distress, and quality. The secondary outcomes were functional performance including physical functioning, activities of daily living, social activities, role performance, and cognitive performance, as well as QOL. Studies that did not examine symptom clusters were excluded.
A comprehensive search strategy consisting of 3 steps was conducted in July 2014. First, a limited search of CINAHL and of MEDLINE was carried out to identify initial keywords relevant to the topic. Second, a more extensive search using the identified keywords was performed to search for potential articles from the following 6 databases: CINAHL, MEDLINE, British Nursing Index, EMBASE, PsycINFO, and Cochrane Library. The keywords used were as follows: cancer, oncology, neoplasm, tumor, carcinoma, psychoeducational intervention, psychoeducational, counseling, psychotherapy, behavioral therapy, coping skill, stress management, relaxation, meditation, patient education, information giving, educational intervention, teaching, social support, psychosocial, symptom cluster, multiple symptoms, and concurrent symptoms. Third, a hand search was conducted to identify additional studies through screening the reference lists of retrieved articles.
One reviewer (W.X.) initiated the literature searching and identified potential relevant articles. After the removal of duplicates, 2 reviewers (W.X. and K.M.C.) independently screened the retrieved records to select eligible studies. If any disagreements occurred between the reviewers, the third reviewer (C.W.H.C.) made the final decision.
QUALITY APPRAISAL, DATA EXTRACTION, AND DATA SYNTHESIS
The 2 reviewers (W.X. and K.M.C.) independently assessed the methodological quality of all included studies, using the Critical Appraisal Skills Program appraisal tool for RCTs.20 Data were extracted independently by the 2 reviewers. Authors of included studies were contacted for any missing data. Any disagreements during the process of quality appraisal and data extraction were resolved by discussion, and the third reviewer (C.W.C.) was consulted. The results of the studies were pooled in a statistical meta-analysis. Continuous outcomes were compared using mean differences and a 95% confidence interval (CI), with a fixed-effect model. If statistical pooling was not appropriate, findings were reported using the narrative synthesis approach.
A total of 240 articles were identified through searching databases and hand searching. Of these, 167 articles remained after removal of duplicates. After reviewing their titles and abstracts, 15 full-text articles were assessed for their eligibility. At that point, 11 articles reporting 9 studies were excluded mainly because symptom clusters were not examined in those studies.15,21–30 Finally, 4 studies were included in the review.8,31–33 A flowchart of the study retrieval and selection process is illustrated in Figure 1.
The methodological quality of most included studies was fair. Most studies had small sample sizes.31–33 Of the 4 included RCTs, 1 study used the method of a lucky draw to randomize patients,8 and the other 3 studies allocated patients through stratification.31–33 Regarding the procedure of blinding, only the data collector was blinded to group assignment in Chan and colleagues’8 study, whereas no blinding was used for the remaining 3 studies.31–33 Blinding and placebo are not always feasible for complex intervention involving active participation of patients. The intervention and control groups in Jarden and colleagues’31 study were not treated equally, as physiotherapy along with the usual care were adopted in the control group. That study used a self-developed instrument without validation as the outcome measurement. The attrition rates of the 4 included studies varied from 2% to 31%; 2 studies reported a large loss to follow-up because of the advanced stage of the disease in patients.8,31 All 4 studies analyzed data based on the intention-to-treat principle. Detailed information of the methodological quality of each included studies is presented in Table 1.
Of the 4 included studies in this review,8,31–33 Chan et al8 used the TOUS to guide the study, Jarden et al31 adopted the Symptom Management Theory34 and TOUS to design interventions, and another 2 studies did not mention which theories underpinned them.32,33 Characteristics of the 4 included studies are described below and are summarized in Table 2.
Participants and Settings
Three hundred forty-three patients with cancer from the 4 eligible studies were included in the review. Sample sizes of each study varied from 42 to 140, but most studies had small samples; only 1 study had more than 100 patients.8 Cancer diagnoses of the participants varied from study to study, including those with lung cancer,8 breast cancer,33 and mixed cancer types32 and patients who were undergoing allogeneic hematopoietic stem cell transplantation, of which 33 of 42 (78.6%) were patients with cancer.31 Two studies were conducted in United States,32,33 1 in Hong Kong,8 and 1 study in Denmark.31
Interventions in terms of their design, components, comparisons, interveners, delivery formats, provision time frames, and duration are described respectively in this part. Two studies tested interventions targeting specific symptom clusters.8,32 They were (1) a symptom cluster of breathlessness, fatigue, and anxiety in Chan and colleagues’8 study and (2) a symptom cluster of pain, fatigue, and sleep disturbance in Kwekkeboom and colleagues’32 study. These 2 clusters were formed based on clinical observation and further verified by examining their internal relationships.35,36 Interventions were designed to treat each single symptom within the 2 clusters. Another 2 studies examined the effects of interventions on post hoc symptom clusters, which were identified using statistical methods after the data collection.31,33 Thus, interventions of these 2 studies were not tailored for any specific symptom clusters in the first place.
All 4 studies adopted behavior therapy as one of the PEI components for patients with cancer. To be specific, Kwekkeboom et al32 adopted only behavior therapy, that is, relaxation, imagery, and distraction exercises. Chan et al8 combined behavior therapy, that is, progressive muscle relaxation (PMR), and education/information. By adopting a mindfulness-based stress reduction program, Lengacher et al33 combined behavior therapy and social support. Jarden et al31 tested an exercise-based multimodal intervention combined with behavior therapy, that is, PMR and psychoeducation. Three studies compared PEI with usual care,8,32,33 and 1 study adopted usual care plus physiotherapy as the comparator.31
The interventions for 3 studies were provided by nurses, in an individual format and during the active treatment period.8,31,32 The remaining study, however, delivered interventions by a clinical psychologist and in a group format and recruited patients who had completed treatment.33 Concerning the duration of interventions, Chan et al8 provided 12 weeks of interventions. Lengacher et al33 conducted a 6-week PEI, whereas in Jarden and colleagues’31 study, interventions lasted 4 to 6 weeks, and patients were followed up until 6 months afterward. Patients in Kwekkeboom and colleagues’ study32 received the shortest period of interventions, only 2 weeks.
Two studies were conducted to manage specific symptom clusters.8,32 Chan and colleagues’8 study used 3 independent instruments consisting of a visual analog scale, the Piper Fatigue Scale, and the State-Trait Anxiety Inventory to measure the intensity of the symptom cluster of breathlessness, fatigue, and anxiety. Kwekkeboom et al32 used the Brief Pain Inventory (BPI), the Brief Fatigue Inventory, and the Pittsburgh Sleep Quality Index to measure the symptom cluster of pain, fatigue, and sleep disturbance. Another 2 studies did not target preidentified symptom clusters.31,33 Conversely, they used generic symptom tools to examine the effects of interventions on post hoc symptom clusters identified after the data collection. Instruments used by them were the M. D. Anderson Symptom Inventory33 and a self-developed Stem Cell Transplantation Symptom Assessment Scale.31
For the outcome of functional performance, Chan et al8 adopted the functional ability subscale of the SF-36 Health Survey to measure functional ability, and the symptom interference subscale of the M. D. Anderson Symptom Inventory was used to measure symptom interference with daily living in 2 studies.32,33 Apart from functional performance, QOL has been acknowledged as another key outcome of symptom clusters.1,4,37–39 The review was intended to examine this; however, none of the included studies measured this outcome.
Effects of Interventions
Because of the heterogeneity of symptom clusters examined in the 4 studies, results of symptom clusters were synthesized in a narrative manner. For the secondary outcome of symptom interference with daily living, a meta-analysis was conducted to combine the results of 2 comparable studies.32,33 Detailed information of various interventions with their effects on outcomes is displayed in Table 1.
Of the 4 included studies, 3 showed statistically significant improvement in symptom clusters for the intervention groups.8,31,32 One study had an significant reduction in symptom severity for 4 of 5 symptom clusters, except the affective symptom clusters (nervousness, anxiety, and stress).31 Significantly improved symptom clusters in these 3 studies included breathlessness, fatigue, and anxiety (P = .003)8; pain, fatigue, and sleep disturbance (P = .032)32; and gastrointestinal cluster (nausea, vomiting, stomach pain, loss of appetite, and diarrhea) (P = .017); cognitive cluster (diminished concentration, memory problems, and fatigue) (P = .002); functional cluster (muscle aches and joint aches) (P = .009); and mucositis cluster (mouth pain, throat pain, and difficulty swallowing) (P = .019).31 All 3 studies8,31,32 adopted PMR as one of the intervention components, and Chan et al8 added patient education. Furthermore, interventions of the 3 studies8,31,32 were all provided by nurses, in an individual format and during the active treatment period; only Chan et al8 continued the intervention after the completion of treatment. Duration of the interventions lasted for 2 to 12 weeks8,31,32; however, in Chan and colleagues’ study,8 the attrition rate was high (27%) at week 12 because of death due to advanced lung cancer.
Symptom clusters in the remaining study were found to be improved; however, the results did not reach statistical significance.33 These symptom clusters included gastrointestinal cluster (nausea, vomiting, lack of appetite, shortness of breath, dry mouth, and numbness), cognitive/psychological cluster (distress, sadness, pain, and remembering), and fatigue cluster (fatigue, disturbed sleep, and drowsy).33 This study combined meditation with social support as its intervention, which was delivered by a clinical psychologist and in a group format.33 The intervention was conducted after the completion of cancer treatment and lasted for 6 weeks.33
With regard to functional performance, the pooled results of 2 studies revealed a statistically significant improvement in the symptom interference with daily living for the intervention group (mean difference, −0.65; 95% CI, −1.22 to −0.09; P = .02) (Figure 2).32,33 Functional ability was also found to be enhanced over time in the intervention group (P = .000).8 None of the included studies measured the outcome of QOL; thus, the effect of PEI on QOL in patients with cancer is unknown in the situation of studying symptom clusters.
Although several publications on symptom clusters could be found over the past decades in cancer nursing, researchers are just beginning to test interventions on the management of symptom clusters. This review is the first to evaluate the effectiveness of PEI on managing cancer symptom clusters, and an extensive search strategy was adopted to include all relevant RCTs.
By reviewing the 4 included studies, PEI seems to be effective in managing symptom clusters and improving functional performance in patients with cancer, of which PMR and patient education were the most commonly used types of PEI. However, the evidence is not conclusive. First, because of the paucity of relevant studies, the sample size of the review was small, which prevented any definitive conclusions. Second, the heterogeneity of symptom clusters examined in the included studies precluded a meta-analysis. One study tested interventions on posttreatment, stable patients with mild intensity of symptoms, which might hide the true effects of interventions.33 In fact, this is the only study that did not detect any statistically significant differences between the intervention and control groups, which may be a false-negative result. Another study had a high attrition rate (27%) at week 12 because of death; thus, the effect of PEI was mainly examined up to 6 weeks, and the long-term effect of PEI was unclear.8 Aside from the intervention, Jarden et al31 did not treat the intervention and control groups equally and used a self-developed instrument without validation to measure outcomes. Not all participants in that study were patients with cancer, and physical exercise, not merely PEI, was a component of the intervention. The findings of the review should be used with caution.
In addition, all 4 included studies focused only on intensity; other dimensions including timing, distress, and quality of symptom clusters were overlooked. Future research needs to measure all the essential dimensions of a symptom cluster in order to understand it more comprehensively.
With respect to the secondary outcomes of functional performance and QOL, only functional performance including symptom interference with daily living and functional ability was measured. One study demonstrated significant improvement in functional ability among patients in the PEI group.8 Symptom interference with daily living was also found to be enhanced when combined in 2 comparable studies.32,33 However, the relatively wide CI (−1.22 to −0.09) of the pooled result increased the uncertainty of the intervention effect, which means further investigations are needed.
Although the evidence is not strong, the results of the functional performance support a view that symptom clusters may have synergistic effects, as suggested by both empirical studies5,37,40 and theories.17,34 The overall structure of the TOUS asserts that influencing factors influence the nature of the symptom experience, which in turn impact the functional performance. Psychoeducational intervention may exert influence on influencing factors or symptoms, or both, to relieve symptom clusters and improve functional performance. However, because of the inadequacy of evidence, further research is needed.
Among the 4 included studies, only two studies8,31 clearly mentioned which theories they used to guide the studies. The 2 theories adopted were TOUS and Symptom Management Theory, which have been used frequently in symptom cluster research. Scientific rigor of research will be strengthened if a study is guided by a theory. Other potential theoretical frameworks related to symptom cluster research include the symptom cluster in children and adolescents with cancer, and the cytokine-induced sickness behavior.39
As noted, 2 studies examined the effects of interventions on post hoc symptom clusters identified after the data collection31,33; thus, interventions were not tailored for any specific symptom clusters a priori. Optimum outcomes may not be obtained in that way. Therefore, it may be more appropriate to identify symptom clusters in advance for intervention studies.
Currently, there are 2 main approaches to identify symptom clusters: clinical and statistical.39,41–43 By using a clinical approach, clusters are clinically predefined, and interrelationships between symptoms within the cluster are tested with analytic techniques. Preidentified symptom clusters targeted by 2 of the included studies in the review were developed in this way.8,32 The main limitation of this approach lies in the subjectivity of symptom selection, and thus, the reliability of results might be challenged.
By adopting a statistical approach, clusters are determined by statistically analyzing a large number of potential symptoms, which assess symptoms more comprehensively. The 2 included studies that identified symptom clusters after collecting data used this approach.31,33 Usually, more than 1 cluster could be generated at a time for a certain study population.39 The priority for interventions should be given to those key symptom clusters that distress patients the most and have great impact on patient outcomes, such as functional performance and QOL. However, limitations also exist in this approach. First, the cluster composition largely relies on assessment tools and the statistical methods used.44 However, there is a lack of comprehensive assessment tools and consensus on optimal statistical methods at present. Second, clinical interpretations for symptom clusters identified in this way might be difficult. Therefore, both approaches are still needed to be investigated to advance the science of symptom clusters.
With regard to interventions for symptom clusters, 2 approaches have been proposed: targeting the individual symptom and targeting the entire cluster.1,3,39 By targeting the individual symptom, an intervention is designed to treat 1 sentinel symptom (eg, pain) within the cluster. A sentinel symptom may acts as a trigger for other symptoms within the cluster; thus, a relieved sentinel symptom may generate beneficial effects for other concurrent symptoms.16,45,46 On the other hand, all symptoms in a cluster are treated by the intervention when targeting the entire cluster. No matter the approaches, an intervention could be developed as either a single intervention or a multimodal intervention. Because a single intervention may benefit all symptoms in a cluster; nevertheless, an individual symptom could also be treated by several interventions.16
The 2 included studies that targeted preidentified symptom clusters adopted the latter approach to treat all symptoms involved.8,32 Moreover, 1 study used only behavior therapy, which is a single intervention.32 The other study adopted a multimodal intervention, combining behavior therapy and education/information.8 Which approach to choose depends on the nature of a symptom cluster, and no recommendations could be made so far for any specific symptom cluster because of limited evidence. A possible burden experienced by patients and clinicians should also be considered when designing interventions.
Managing symptom clusters instead of single symptoms is considered to be a contemporary approach in cancer care.8 The present review suggests a potential role of PEI in managing cancer symptom clusters. For practice, we hope this review could enhance clinicians’ awareness of managing symptom clusters using PEI to yield more effective and efficient cancer care. The priority should be given to those key symptom clusters that distress patients the most. Provision by nurses, in an individual format and during the active treatment period, may be useful strategies for delivering PEI. Regarding the effective duration of PEI, the findings were inconclusive. However, 6 weeks seems to be a feasible and suitable period for implementing PEI.
For research, there is an urgent need for investigators to test PEI on various types of cancer symptom clusters. Scientifically rigorous studies focusing on some commonly used PEI such as PMR and patient education are warranted. Large-scale, tailored, and theory-driven research is preferable. Furthermore, key patient outcomes for symptom clusters such as functional performance and QOL should be measured to evaluate the intervention’s clinical significance. Lastly, the sustainability of PEI is also worth investigating. Among the 4 included studies, only 1 study followed patients up to 6 months after the intervention.31 However, as a dynamic construct, symptom clusters may change over time.44 This is a possible reason for the researchers to find it difficult to conduct intervention studies for symptom clusters. Another difficulty lies in the variability of symptom clusters experienced by each patient in terms of the prevalence and intensity of individual symptoms within a cluster.47 Future intervention studies may need to take these challenging issues of managing symptom clusters into consideration.
Although research on symptom clusters has been greatly emphasized in the area of cancer symptom management, studies that test interventions targeting symptom clusters are rare. Psychoeducational intervention appears to be efficacious in managing symptom clusters in patients with cancer. However, no definitive conclusions could be drawn because of the small sample size and heterogeneity of symptom clusters examined in this review. Future well-designed investigations testing some commonly used PEI such as PMR and patient education on various types of cancer symptom clusters are warranted.
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