This study is the first to compare the number and types of symptom clusters identified using pediatric oncology patients’ ratings of symptom occurrence and severity. The groupings of symptoms identified in the EFA analyses are clinically meaningful and were confirmed in the latent variable analysis. With the exception of cough and sweating, the symptoms in the chemotherapy sequelae cluster are among the most common physical symptoms associated with chemotherapy administration. The mood disturbance cluster was limited to psychosocial symptoms. Most of the symptoms in the neuropsychological discomforts cluster (i.e., all except hair loss, altered self-perception, and skin changes) are associated with the sickness behavior syndrome that is observed following the administration of pro-inflammatory cytokines.48–50
These findings have direct implications for clinical care. In this study, 8 symptoms clustered in the chemotherapy sequelae cluster in the analyses based on symptom severity (11 symptoms when analyses were based on symptom occurrence). The complexity of this configuration may be perplexing to clinicians and researchers. However, the symptoms made variable contributions to this cluster, as noted by the estimates for the exploratory measurement model. Notably, nausea and vomiting made the strongest contributions to this cluster, and may be particularly important targets for nurses when planning symptom management interventions in the clinical setting or designing intervention research. Additionally, nurses may direct interventions towards the symptom in a cluster which is most amenable to treatment, with the potential of concurrent treatment of symptoms in the cluster which are more difficult to treat. For example, strategies to ameliorate worry (e.g., provision of clear and accurate anticipatory guidance) may be effective in decreasing feelings of sadness. In the SMT, this approach addresses the “what” query of the symptom management component. Nurses in the clinical setting may be best poised to identify patterns in symptom management that warrant further evaluation by researchers. In addition, considering the constellation of symptoms in the neuropsychological discomforts cluster, further investigation of the potential association of cancer-related symptoms with cytokines or other biologic mechanisms is warranted. Such investigation may ultimately lead to discoveries of new pharmacologic therapies for these untoward effects.
Direct comparisons across pediatric and adult studies are difficult because different symptom inventories were used, and the total number of symptoms varies across instruments. Symptom inventories may evaluate as few as 8 to 10 symptoms (e.g., the M.D. Anderson Symptom Inventory,51
the Symptom Distress Scale52
). The MSAS 10–18 with 31 symptoms was used for this study to maximize the cluster configurations. However, constellations of symptoms within a cluster are likely to differ if a symptom inventory with only 8 items versus 31 items is used to evaluate for symptom clusters.
In addition, comparisons across studies are difficult when patients are enrolled at different points in their treatment trajectories (e.g., on or off therapy) and at different points within a treatment cycle (e.g., at the start of a chemotherapy cycle or at blood count nadir). All patients in this study were enrolled at the start of a myelosuppressive chemotherapy regimen to minimize variability. No similar trials (i.e., investigations of symptom clusters exclusively among patients receiving chemotherapy) were noted in the pediatric oncology literature. Considering the early stage of these investigations in pediatric oncology, the lack of comparable studies among children with cancer is not surprising. With this in mind, one might look to the symptom clusters literature in adult oncology for lessons learned. However, despite the publication of a large number of symptom clusters studies among adult cancer patients, only three studies were found in which chemotherapy was uniformly administered.53–55
These studies show few similarities in their symptom cluster configurations. These disparities may be expected as none of these studies structured data collection around a common point in patients’ chemotherapy cycles, with recall periods up to one month.
Differences in the choice of symptom dimension used in the statistical analysis (e.g., occurrence, severity, distress) have the potential to affect study results. In this study, notable similarities were found between the symptom clusters identified based on symptom occurrence and severity ratings. The most striking commonalities were found in the mood disturbance cluster and is congruent with previous studies.56, 57
For example, Kim and colleagues reported similarities in occurrence and severity symptom cluster analyses among breast and prostate cancer patients during radiotherapy.56
In a study by Suwisith and colleagues,57
the symptom clusters based on severity ratings were quite similar to those based on distress ratings among women receiving chemotherapy for breast cancer. Comparisons between data sets based on occurrence and severity may not be ideal. However, symptom clusters research is an emerging field, and at times researchers must rely on such comparisons across symptom dimensions if studies with analyses based on similar dimensions are not available.
Finally, numerous statistical analyses have been utilized in prior studies. Consensus on the most robust statistical analysis to use to evaluate for symptom clusters has not been reached. However, Skerman recommends the use of EFA or hierarchical cluster analysis when researchers’ goals are to identify unknown groupings of symptoms from an array of symptoms and the use of confirmatory factor analysis to validate hypothesized clusters of symptoms.11
Despite the difficulties in comparing studies based on disparate methodologies as outlined above, variations on the common symptom cluster of fatigue, sleep disturbance, pain and depression are noted in the studies with the most similar patient populations (i.e., children or adolescents with cancer,5, 8
and adults receiving cancer chemotherapy53–55
). In our study, we noted an association between pain, feeling drowsy, insomnia (in the analysis based on symptom occurrence only), and lack of energy (in the analysis based on symptom severity only). Feelings of sadness clustered with other psychological symptoms (i.e., with feeling nervous, worry, feeling irritable). Among the pediatric studies, both Tseng and colleagues8
and Yeh and colleagues5
reported an association between fatigue, sadness (or psychological distress), and disturbed sleep, while pain clustered with taste changes5
or grouped as a single symptom.8
Aprile and colleagues53
reported an association of pain and fatigue among adults with cancer, while depression clustered with anxiety. These researchers based symptom occurrence on medical record review. Sleep disturbance and insomnia were not included in the cluster configuration, as they were rarely abstracted from patients’ charts (but likely were significant issues for hospitalized patients). Skerman and colleagues54
reported the association of sleep, fatigue, and pain. However, no psychosocial variables were evaluated in this study. Thus the relationship of depression to other variables cannot be determined. Yamagishi and colleagues55
reported the association of fatigue and sleep, while pain clustered with dyspnea and numbness and psychological distress was grouped as a single item. None of these studies reported the complete constellation of fatigue, sleep disturbance, pain and depression. The inconsistencies in the clustering of depression or feelings of sadness are not surprising when one considers the extreme variability in the inclusion of psychosocial variables among the groups of symptoms being evaluated in these studies. Feelings of sadness or depression was one of numerous psychosocial variables included in some studies,5, 53
was listed as “psychological distress” in others,8, 55
and was not evaluated in another.54
In addition, psychological symptoms have many different connotations which vary considerably based on the verbiage chosen for particular symptom checklists. Likewise, the clustering of pain varied among these studies. The heterogeneity in the types of pain experienced during cancer treatment (e.g., procedure-related pain, chronic, disease-related pain) may contribute to these findings. Nevertheless, the overall consistency of the clustering of fatigue, sleep disturbance, pain and depression emphasizes the importance of addressing these symptoms in clinical practice and in additional research. When conducting symptom cluster research it is critical to include these four symptoms and a wide range of additional psychosocial symptoms in order to best delineate the relationships among a large number of variables.
According to the SMT, multiple perceptions of the symptom experience must be considered (e.g., the perception of the patient and that of the clinician), with the potential for discordant evaluations. These incongruences can lead to difficulties in symptom management.58
The patients’ perspective is considered to be the gold standard. However, in pediatrics, parental concerns are often brought to the foreground and may be in conflict with patients’ reports. In this investigation the adolescent patients’ perspectives were analyzed. Future analyses could compare symptom cluster constellations based on parental report to those based on patients’ reports to gain insight into factors that influence the effectiveness of symptom interventions.
Limitations of this study include the relatively small sample size and the use of a very heterogeneous sample with regards to cancer diagnoses, the chemotherapy agents used, and the time elapsed since the patients’ diagnoses. The chemotherapy sequelae cluster may have a very different configuration (e.g., fewer symptoms than the 8 symptoms noted in the current investigation) if a symptom inventory was administered to a more homogeneous sample in terms of cancer diagnosis, chemotherapy regimen, and/or treatment cycle. In addition, this study was a cross-sectional analysis during a single chemotherapy cycle. Therefore, changes in symptom clusters over time were not evaluated. The KPS was used to measure patients’ functional status. Although this scale was used in pediatric oncology research, psychometric evaluation of the measure in pediatric studies has not been published. Finally, a one week recall period was used to evaluate symptoms. Anecdotally, some patients reported difficulties in recalling and/or summarizing events during the past week due to the variable nature of the symptoms.
Despite these limitations, to our knowledge this study is the first to evaluate symptom clusters based on a standardized time point in relation to chemotherapy administration. The nature of symptom patterns following myelosuppressive cancer chemotherapy adds credence to our conceptual approach of evaluating patients at similar points in their chemotherapy schedules. With significant variability in analytic approaches to symptom clusters research, a state of the science summit for key researchers to debate these issues and make recommendations may promote uniformity in forthcoming investigations.