Correlation Analysis of Mood State and Symptom Clusters in Patients With Stage- Lung Cancer During Immunotherapy


 Purpose: To investigate the status of symptom clusters and mood states and analyze the correlation between them in patients with stage-IV lung cancer undergoing immunotherapy.Methods: Using a convenience sampling method, we selected 259 patients for analysis with stage-IV lung cancer who were admitted to the oncology department of a hospital for immunotherapy from February to December 2020. Three instruments were used: a general situation questionnaire, the Chinese version of the M. D. Anderson Symptom Inventory, and the Brief Profile of Mood State Short Form.Results: An exploratory factor analysis identified three main symptom clusters: the disturbance influence, general, and pain–fatigue related symptom clusters. The total score for mood state was (25.71 SD: ±8.32). The score of the depression dimension was the highest (3.30 ±1.85) in the negative mood state; the total score of mood state and the score of negative mood state at different latitudes were significantly positively correlated with the total score of symptom clusters (r = 0.420–0.529, p < 0.01).Conclusion: There are many symptom clusters in patients with lung cancer undergoing immunotherapy. The negative mood state is significant and changes along with changes in symptom clusters; moreover, there is high correlation between them. There should be more focus on the evaluation and management of symptom clusters of patients in nursing to improve the patients’ quality of life.


Introduction
Among malignant tumors, lung cancer has the highest incidence and mortality globally [1]. It is one of the most common malignant tumors in China, and in the past 40 years, its mortality has been the highest and it has been increasing year by year [2]. Most patients are already at an advanced stage by the time of diagnosis, which affects the mood state of patients to different degrees and in uences their physical and mental health. The concept of mood state comprises a positive mood state and a negative mood state. Positive mood state is mostly manifested in two aspects: high spirits and happiness. Negative mood state includes depression, fatigue, tension, distress, and panic. Mood states that are contagious and last for a long time are patients' emotional or affective responses to their situations and treatments. These situations can cause negative emotions and in uence the patients' physical and mental health, attitude, and behavior for a long time.
After chemotherapy and molecular targeted therapy, the treatment of lung cancer has now entered a new era: that of immunotherapy represented by immune checkpoint inhibitors. Chemotherapy combined with immunotherapy has become a clinically effective therapeutic method of prolonging the life of patients with advanced lung cancer [3]. However, the toxic side effects of the treatment process increase patients' physical and psychological discomfort, leading to different degrees of symptom pressure [4]. Negative mood has an adverse effect on the quality of life of patients [5]. To date, the relationship between symptoms and mood state has not been appropriately investigated.
Therefore, this study analyzes the correlation between symptom clusters and mood states of patients with lung cancer during immunotherapy and provides evidence for clinical nursing staff for appropriate symptom management. Our ndings could play a vital role in the clinical practice of symptom management and nursing practice to improve the quality of life of patients with advanced lung cancer. This questionnaire was designed by researchers to obtain the patients' basic information, including age, gender, religious belief, education level, marital status, place of residence, disease course, monthly household income, payment method of medical expenses, and occupational status.

MDASI-C
The scale was developed by the University of Texas M. D. Anderson Cancer Center in 2000 and has been translated into 29 languages (including Chinese). This study draws on the MDASI-C scale developed by Zang Yu of the Southern Medical University [7]. The rst part of this scale comprises 13 questions to assess the severity of patients' common symptoms experienced during the previous day. The second part includes six options to mainly evaluate the level of in uence symptoms have on the life of patients with cancer. Each item is scored on a numerical scale ranging from 0 to 10, in which 0 indicates no symptoms and 10 very severe symptoms. The internal consistency reliability was 0.84-0.86, con rmed through 20 pretests with a small sample size.

BPOMS-SF
The Chinese version of the BPOMS-SF [8,9] was compiled by American scholar McNair and revised by Professor Chi Song of the Brain Behavior Research center at the Chinese Academy of Sciences. It comprises 30 items in six dimensions: (1) tension (T), (2) depression (D), (3) anger (A), (4) fatigue (F), (5) confusion (C), and (6) vigor (V). Among them, vigor is a positive mood state, while the other ve dimensions are negative mood states; these are measured on a ve-point Likert scale from 0 = not at all to 4 = very much. The total score is the scores of the ve negative mood states minus the score of the positive mood state. The higher the score, the greater the degree of psychological distress. This scale is widely used in clinical evaluation, sports, and scienti c research to measure the mood, emotion, and emotional state of the individual. The scale has good reliability [9,10]. In this study, 20 pretests with a small sample size showed that the total Cronbach's alpha of the scale was 0.756 and the internal consistency reliability was 0.705-0.892.

Statistical Methods
An MS Excel database was established for data input and treatment, and SPSS 22.0 software was used for the analysis. The measured data were described by mean and standard deviation (SD), and the enumeration data were described by percentage. The internal consistency coe cient was used to describe the scale's reliability. The scale's exploratory factors were analyzed by principal component analysis. A Pearson's correlation analysis was used to describe the correlation between variables.

Factor Loadings Analysis of Symptom Clusters
An exploratory factor analysis was used to extract patient symptom clusters. Moreover, a principal component analysis and varimax rotation were conducted.
The principle of factor extraction involved symptoms with incidence rate ≥ 20%, characteristic value > 1, and factor loading ≥ 0.5. The results showed that four common factors were obtained and the accumulated variance contribution was 67.10%. Factors 1-4 included the disturbance in uence, general, pain-fatigue related, and gastrointestinal symptom clusters (see Table 3).

In uence and Analysis of Patient Symptom Clusters on Life
The median score of the patient symptom clusters' in uence on life was 3-4 and the incidence rate was 52.12-67.95%. The in uence on life in the order of high to low was mood (67.95%), general activity (64.86%), daily work (62.16%), enjoyment in life (59.07%), walking ability (54.83%), and relationship with others (52.12%). The order of severity from high to low was mood, general activity, daily work, enjoyment in life, walking ability, and relationship with others. See Table 4 for speci c scores.

Correlation Analysis of Mood State and Patients' Symptom Clusters
A Pearson's correlation analysis was conducted between the total scores of the mood state and scores of all dimensions and the scores of symptom clusters in patients with lung cancer. The total scores of the mood state and scores of other dimensions except vigor were shown to be signi cantly positively correlated with the scores of symptom clusters (r = 0.420-0.529, p < 0.01). The scores of the disturbance in uence, general, pain-fatigue related, and gastrointestinal symptom clusters were closely and positively correlated with the total scores of the mood states (r = 0.304-0.516, p < 0.01), as shown in Table 6.  [17]. Table 4 shows that symptom clusters have a certain impact on the life of patients, with the incidence rate ranging from 52.12-67.95%. Based on severity, the order from high to low is mood, general activity, daily work, enjoyment in life, walking ability, and relationship with others. All patients in this group have advanced lung cancer, have experienced multiple chemotherapies, and continue to search for updated therapeutic schemes to prolong the survival period. The uncertain outcome of immunotherapy affects the mental and emotional reactions of the patients, causing anxiety, worry, depression, or distress and feeling of losing the enjoyment in life, and even affecting interpersonal communication. Because of the existence of multiple physical and mental symptoms, the patients' activities, work, and daily life are affected, and some patients have problems in communicating with their family members.
The mood state of the patients in this group was found to be good. Table 5 shows the total score of the mood state (25.71 ± 8.32). Based on their scores, the order of negative mood dimensions from high to low is depression, fatigue, tension, anger, confusion, vigor. The situation is optimistic -better than the previous literature reports [18]. This may be related to long illness time, regular chemotherapy, continuous professional guidance from doctors and nurses, health education, and psychological care. Judging from the psychological reaction process of patients with tumors, advanced patients have already gone through the fear, doubt-denial, and depression stages [19]. With the progress of radiotherapy, chemotherapy, targeted therapy, and current immunotherapy, patients have entered the adaptation stage; however, the depression dimension is more serious. The negative, over-generalized, and self-reproaching thinking naturally leads to a depressing sense of despair. The depressed mood state, which is the core of other negative emotions, leads to negative thinking. Therefore, the negative viewpoint of patients with cancer ampli es the painful experience. When the patients' mood hits rock bottom, their thinking enters another mode. The bad mood state dominates their attitude toward negative events, which may lead to extreme negative emotions such as tension and anger.
This research shows that the total score of the mood state, tension, depression, anger, fatigue, and confusion of patients are highly positively correlated with the total score of symptom clusters (r = 0.420-0.529, p < 0.01); moreover, the total score of the mood state is highly positively correlated with the total score of the disturbance in uence, general, pain-fatigue related, and gastrointestinal symptom clusters (r = 0.304-0.516, p < 0.01). Relevant studies show that symptom clusters have an important in uence on the quality of life of patients with lung cancer, and the emotional symptoms are independent factors in uencing quality of life. The more severe the symptom clusters of patients, the less satisfactory the quality of life [16,17,20]. For patients with advanced cancer, if the symptoms cannot be alleviated, the patients' prognosis, such as mood state and quality of life, will be affected by many negative emotions [5]. In particular, worries about things such as diseases, desire for treatment, and tolerance to adverse reactions will be internalized into the patients' emotional symptoms. Symptom clusters such as sadness and distress are a type of negative feeling that patients with lung cancer often experience in the late stage of the disease. The uncertainty of the therapeutic effects of most new immunotherapy drugs makes patients prone to anxiety and uneasiness, thus aggravating the negative mood state. Because tumor metastasis can cause more pain and fatigue, which will lead to a decline in patients' vigor, cause a lack of spirit, and affect daily activities and quality of life, it is very unfavorable to the rehabilitation and treatment of patients.
A longitudinal study conducted by the University of California in the United States shows that there are six symptom clusters in patients with lung cancer receiving chemotherapy. The symptom clusters change with time and the patients' experience also changes. However, three symptom clusters remain relatively stable: lung cancer-speci c, psychological, and nutritional symptom groups [21]. It is suggested that medical staff should pay close attention to the psychological changes in patients with lung cancer at various treatment stages. Appropriate psychological counseling and psychological nursing can help alleviate the patients' experience symptom clusters to improve their negative mood [22].

Conclusion
Patients with lung cancer experience many symptom clusters during immunotherapy. The negative mood state is a serious issue and it changes along with the change in symptom clusters; there is high correlation between symptom clusters and mood state. In clinical nursing work, medical staff should pay close attention to the mood state of patients with lung cancer undergoing immunotherapy treatment and the interaction between various symptom clusters, so as to actively address and solve them. This will guide patients and their family members to learn to manage symptoms of symptoms, actively participate in rehabilitation activities of various social groups, establish anti-cancer con dence, and improve mood state.
This study has certain limitations. As this survey was carried out in a specialized Grade-A tertiary hospital, the ndings do not have broad applicability. Moreover, research on patient symptom clusters during immunotherapy is still in the initial stage. To effectively manage and intervene in patient symptom clusters, future research should investigate the model characteristics of relevant symptom clusters and establish appropriate intervention modes to reduce the physical and mental burdens of patients and improve their quality of life.