Plain English summary
Patients with lung cancer undergoing chemotherapy often face a diminished Health-related Quality of Life (HRQoL) and a substantial symptom burden. While prior research predominantly concentrated on individual symptoms and overall quality of life, symptoms tend to cluster, thereby amplifying their impact on HRQoL. Given the multifaceted nature of HRQoL, it is imperative to conduct a comprehensive analysis of each domain, as an aggregate score may fail to capture the complete picture. Consequently, this study aimed to identify symptom clusters in lung cancer patients undergoing chemotherapy and explore their correlation with HRQoL. Three symptom clusters were identified: Somato-psychological (encompassing pain, fatigue, sleep disturbance, distress, drowsiness, and sadness), Respiratory (involving shortness of breath, coughing, expectoration and chest tightness), and Gastrointestinal (including nausea, poor appetite, vomiting, constipation, and weight loss). The Somato-psychological SC and Gastrointestinal SC negatively impact patients' HRQoL. Health care providers should prioritize these SCs to identify high-risk patients early and implement targeted preventive and intervention measures for each SC.
Introduction
Lung cancer is a significant contributor to global cancer incidence and cancer-related mortality, with 2,206,771 new patients with lung cancer and 1,796,9144 deaths in 2020 [
1]. It has the highest incidence and death rate among men and shows a persistent increasing trend [
2]. Owing to its heigh incidence rates and substantial number of patients, lung cancer has become a prominent public health challenge [
3]. Lung cancer patients lack distinct features in their early stages, making them easily overlooked. Therefore, it is often diagnosed at advanced stages, and is accompanied by severe symptom burden [
4]. In addition to the severity of disease characteristics, treatment also plays a crucial role. While immunotherapy and targeted therapy are emerging, chemotherapy remains the mainstream treatment [
5]. Chemotherapy, a nonspecific chemotherapeutic drug, not only inhibits the growth of tumor cells but also affects normal cells, causing a range of side effects, such as pain, fatigue, vomiting, and numbness [
6].
When Miaskowski and Dodd introduced the concept of symptom clusters (SCs), medical professionals gradually recognized that symptoms frequently did not manifest in isolation but rather presented as clusters, multiplying their impact on patients [
7,
8]. Previous studies have identified several SCs. In patients with lung cancer undergoing chemotherapy, the number of SCs ranges from three to five. Common SCs include the somatic SC (mainly including pain, fatigue, and sleep disturbance), the psychological SC (primarily consisting of sadness, distress, and feeling nervous), and the respiratory SC (also known as the lung cancer-specific SC, comprising coughing, expectoration, chest tightness, hemoptysis, and shortness of breath) [
9‐
15]. In our previous study of patients receiving chemotherapy, we also identified respiratory SC, gastrointestinal SC, and somatic SC [
9,
15]. In patients receiving immunotherapy, Yang [
16] identified five SCs: lung cancer-related, emotional-related, physical, skin, and neural SCs. In patients after CT-guided microwave ablation (MWA), Liu et al. [
17] measured symptoms at 24, 48, and 72 h post-MWA. They identified four SCs: MWA-related, somatic, respiratory, and gastrointestinal SCs. These SCs persisted across the three time points, although the specific symptoms within each cluster varied slightly. These uncomfortable SCs directly affect patients' HRQoL [
18,
19]. Different treatment methods for patients can lead to variations in the identified SCs. A gold standard for identifying SCs has not yet been established, and larger sample studies are needed to confirm the classification of SCs in lung cancer patients undergoing chemotherapy.
Health-related quality of life (HRQoL) encompasses a comprehensive concept, including physical health, psychological state, level of independence, social relationships, and relationships with essential elements in the environment [
20]. It has the potential to predict disease prognoses and patient mortality [
21]. Therefore, understanding the HRQoL of patients is crucial for assessing the overall impact of treatments and care interventions. The HRQoL of patients with lung cancer is generally lower than that of patients with other malignancies [
22,
23]. Some studies have explored the relationships between symptom clusters and HRQoL in lung cancer patients, and reported that symptom clusters negatively impact HRQoL during chemotherapy, surgery, immunotherapy, and targeted therapy [
11,
16,
24‐
27]. Although the above studies revealed that SCs might reduce HRQoL, they all used exploratory factor analysis to identify SCs, which does not account for the interrelationships between symptoms. Moreover, the sample sizes for these studies were relatively small. Therefore, this study aims to (1) use network analysis to identify SCs in lung cancer patients undergoing chemotherapy and (2) analyze the impact of each SC on HRQoL and each of its functions.
Discussion
This study identified three SCs: the Somato-psychological SC (including pain, fatigue, sleep disturbance, distress, drowsiness, and sadness), the Respiratory SC (including shortness of breath, coughing, expectoration, and chest tightness), and the Gastrointestinal SC (including nausea, poor appetite, vomiting, constipation, and weight loss). These results were consistent with those of the SCs previously identified by our research team [
9,
15]. The first SC was the Somato-psychological SC. Some studies have divided this SC into two separate SCs, the Somato SC and the Psychological SC, but the primary symptoms of these SCs mostly include fatigue, sleep disturbance, and sadness [
10,
11,
13,
14]. This result suggests that physiological discomfort and psychological distress may share common biological causes or have a synergistic relationship. The study results also indicated that the central symptom of the Somato-psychological SC was fatigue. A systematic review and a study of 1330 patients with 7 types of cancer also identified fatigue as the most common and central symptom [
12,
39]. This situation highlights the need for health care providers to pay particular attention to fatigue symptom [
40].
The second SC was the Respiratory SC. Some studies have referred to the SC as the lung cancer-specific SC [
10,
13,
14,
16]. The components of this SC are generally consistent, mostly comprising respiratory-related symptoms such as shortness of breath, coughing, expectoration, and chest tightness. Yang [
16] identified a lung cancer-related SC in patients receiving immunotherapy, which included weight loss, shortness of breath, cough, lack of appetite, and fatigue; the differences may be due to variations in treatment protocols. Li [
11] included hemoptysis in the Respiratory SC, but in this study, the prevalence of hemoptysis was low and not closely related to other symptoms; thus, it was not included in the SC. The central symptom identified in the Respiratory SC was coughing. A qualitative analysis also suggested that coughing plays a central role in the Respiratory SC [
41]. The result may be because coughing consumes more oxygen, increasing the respiratory rate and depth, thereby affecting chest tightness and shortness of breath [
42].
The final SC was the Gastrointestinal SC. The symptoms associated with this SC are relatively consistent and primarily include nausea, poor appetite, vomiting, and constipation. Russell [
13] and Wong [
14] used the MSAS questionnaire to survey lung cancer patients undergoing chemotherapy and referred to this SC as the nutritional SC, which included decreased appetite and weight loss. This study used the MDASI for the survey, and the results were similar. The central symptom identified in the Gastrointestinal SC was vomiting. However, research specifically focusing on central symptoms is limited, and the central symptoms for lung cancer patients undergoing chemotherapy require further validation. In summary, the SCs identified in this study are consistent with those identified in most previous studies. While there may be some differences due to the treatment methods, the majority of symptoms are the same.
The results of this study indicated that the global health status score was 59.71 ± 21.09, which is lower than the normative scores reported by Nolte (66.1 ± 21.7) [
43], Young (62.3 ± 23.7) [
44], and Pilz (68.2 ± 20.1) [
45] for the general population. This decrease in HRQoL was attributed to the study population being composed of lung cancer patients, whose HRQoL was diminished due to the disease. Compared with that of other cancer patients, the HRQoL of the lung cancer patients in this study was lower, similar to the findings of Wan (56.9 ± 24.6) [
46] and Machingura (60 ± 22) [
47]. This disparity may be due to the more severe side effects of lung cancer treatment than other types of cancer, resulting in a lower HRQoL [
48]. However, compared with other studies, our results indicated a higher HRQoL [
49,
50]. This improvement is likely due to better medical conditions and continuous advancements in medical technology and treatment methods, leading to an increased HRQoL for lung cancer patients compared with that reported in the past [
51,
52].
The results of this study indicated that the Somato-psychological SC negatively affected the global health status and all five functional domains of HRQoL, which is consistent with previous findings [
11,
16,
27]. Additionally, our study revealed that the Somato-psychological SC was the primary predictor of patients' HRQoL. The Somato-psychological SC included various physical symptoms (such as fatigue and pain) and psychological symptoms (such as distress and sadness). Discomfort, such as fatigue, pain, and sleep disturbances, directly reduces patients' physical functioning and participation in life activities [
53,
54]. Negative emotions such as distress and sadness can affect patients' social activities, work ability, and overall life satisfaction [
48,
55]. The multidimensional impact of these symptoms significantly influences patients' HRQoL, making the Somato-psychological SC the most impactful for their HRQoL.
The Gastrointestinal SC negatively impacted global health status, physical functioning, role functioning, emotional functioning, and cognitive functioning, which is consistent with previous research findings [
11,
56]. Gastrointestinal symptoms such as nausea and vomiting could lead to poor appetite and malnutrition, limiting patients' activity levels and affecting their ability to work, engage in hobbies, or participate in leisure activities [
57,
58]. Consequently, these factors reduce patients' HRQoL. Li et al. [
11] reported that the Gastrointestinal SC negatively affects patients' social functioning. However, in this study, the Gastrointestinal SC did not significantly impact patients' social functioning. This discrepancy could be due to the strong familial support influenced by traditional Chinese filial piety, which provides stable social support for most cancer patients [
59,
60]. Additionally, the widespread use of advanced online communication tools allows patients to communicate seamlessly across time and distance, mitigating the impact of the Gastrointestinal SC on social functioning [
61,
62].
In this study, the Respiratory SC did not impact patients' HRQoL, whereas previous research indicated a negative impact [
11,
16,
26]. The inconsistency could be attributed to the fact that most patients receive treatment, thereby reducing the severity of respiratory symptoms compared with other SCs and influencing factors. This reduced impact may not significantly affect patients' HRQoL. Future research could explore the specific effects of the Respiratory SC on HRQoL through subgroup analysis or long-term follow-up studies involving different patients.
In addition, the findings indicated that patients with higher incomes had higher scores in all five functional domains. Patients who were still employed presented higher scores in role functioning, emotional functioning, and cognitive functioning compared to those who were not employed. Age negatively affected physical, role, and cognitive functioning, but positively affected emotional functioning. Although the above demographic characteristics could influence patients' HRQoL, the impact of SCs was the most significant. Therefore, health care providers should be encouraged to perform personalized assessments and health guidance for SCs. Interventions should be implemented for the Somato-psychological SC and the Gastrointestinal SC, such as exercise and psychosocial interventions for the Somato-psychological SC, and dietary care along with nutritional management for the Gastrointestinal SC, to maximize improvements in patients' HRQoL.
Limitations
The current study was a cross-sectional correlational investigation. While a significant reduction in symptoms may lead to improvements in certain functional domains, deterioration in function could also result in more frequent or severe symptoms. However, the cross-sectional design of this study limited our ability to establish causality. Therefore, future research should consider longitudinal prospective studies to validate whether symptom improvement indeed predicts better HRQoL.
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