Factors influencing cancer-related fatigue in patients with esophageal cancer undergoing radiotherapy:pathway analysis

doi:10.21203/rs.3.rs-4690950/v1

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Research Article

Factors influencing cancer-related fatigue in patients with esophageal cancer undergoing radiotherapy:pathway analysis

https://doi.org/10.21203/rs.3.rs-4690950/v1

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Background

Cancer-related fatigue in patients with esophageal cancer significantly impacts their five-year survival rate and causes serious distress to their physical and mental condition.Therefore, it is crucial to pay attention to the current status of fatigue in esophageal cancer patients in order to reduce their physiological and psychological distress.As a positive psychological trait, self-efficacy can influence the level of fatigue in patients undergoing radiotherapy for esophageal cancer. However, the pathways by which self-efficacy affects cancer-related fatigue remain unclear.

Objective

To investigate the factors influencing cancer-related fatigue in patients undergoing radiation therapy for esophageal cancer, and to investigate the role of social support as a mediator between self-efficacy and cancer-related fatigue using the theory of unpleasant symptoms.

Methods

The study used a descriptive survey approach, and data were collected at a tertiary hospital in Nanjing between October 2022 and May 2023. 225 patients with esophageal cancer undergoing radiotherapy completed the Cancer-Related Fatigue Scale, Self-Efficacy Scale, and Social Support Rating Scale.Correlation analysis and multiple linear regression analysis were used to analyze the data;the pathways through which self-efficacy influences cancer-induced fatigue were analyzed using the SPSS PROCESS program.

Results

There was a strong negative correlation between cancer-related fatigue and self-efficacy (r = -0.948; P < 0.05). The results of the mediation effect test indicated that social support partially mediated the relationship between self-efficacy and cancer-related fatigue (β = -0.342, P < 0.01). Furthermore, the mediating effect (− 0.342) accounted for 36.08% of the total effect (− 0.948).

Conclusion

Our findings confirm a negative correlation between cancer-related fatigue and self-efficacy in patients undergoing radiation therapy for esophageal cancer. Social support serves as a mediating factor in reducing fatigue by enhancing patients' self-efficacy.

Esophageal cancer

Radiotherapy

Cancer-related fatigue

Social support

Self-efficacy

Influencing factors

Pathway analysis

In 2020, the number of new cases of esophageal cancer and related deaths in China was about 324,000 and 301,000, with some of the highest morbidity and mortality rates.¹Radiation therapy is one of the main treatments that kills tumor cells and also damages the esophageal tissues, causing great physical and mental distress to patients and leading to a high incidence of cancer-related fatigue.²Cancer-related fatigue (CRF) is a subjective sensation of fatigue or depletion, including somatic, emotional, or cognitive aspects, resulting from the cancer itself or from cancer-related treatments.³A study has analyzed the symptom clusters of esophageal cancer patients during the peri-radiotherapy period, indicating that fatigue symptoms were consistently present throughout the radiotherapy period and showed a trend of continuous worsening.⁴A previous study has demonstrated that the level of fatigue in esophageal cancer patients significantly impacts their five-year survival rate and causes serious distress to their physical and mental condition.⁵Therefore, it is crucial to monitor the current status of patient fatigue to alleviate their physical and mental distress.The theory of unpleasant symptoms suggests that an individual's distress from symptoms is caused by a confluence of physiological,psychological,and social elements.⁶As a positive psychological trait, self-efficacy can influence the degree of fatigue in patients undergoing radiotherapy for esophageal cancer.^7,8However, the pathways by which self-efficacy affects CRF are unclear.The present study aims to examine the factors that affect CRF in patients undergoing radiation therapy for esophageal cancer. Additionally, the theory of unpleasant symptoms will be used to examine the function of social support as a mediator between self-efficacy and CRF.

2.1. Study and sample

The present study employed a descriptive survey design and data collection was conducted between October 2022 and May 2023. Analyses were conducted on the patient's demographics, self-efficacy scale, cancer-related fatigue scale, and social support rating scale.The following were the inclusion criteria: 1)individuals receiving radiation therapy and meeting the diagnostic criteria for esophageal cancer;2)age of ≥ 18 years; 3)capacity to communicate and read; and 4)capability to volunteer to participate. Patients who met other severe criteria, such as malignant tumors or major conditions affecting the heart, brain,liver,kidney,or lung, were excluded.

2.2. Assessment instruments

2.2.1. Demographic characteristics

The study used self-designed demographic characteristics to collect data from participants, such as age,gender,education level, marital status,monthly household income,type of medical insurance,tumor stage,duration of illness,number of radiation treatments,sleep quality,and comorbidity with chronic diseases. Based on previous studies, these factors were selected.

2.2.2. Cancer-related fatigue

The patients' levels of cancer-related fatigue were assessed using the Chinese Cancer-Related Fatigue Scale (CFS). Zhang et al. translated and refined the Cancer-Related Fatigue Scale, building on the work of Okuyama et al.^9,10There are fifteen things total, divided into three categories: cognitive, emotional, and physical fatigue. A five-point Likert scale, ranging from 1 (no fatigue) to 5 (very fatigue), was used to score the responses. The CFS score, which varied from 0 to 60, indicated the degree of cancer fatigue. The Cronbach's alpha for the CFS was 0.82.

2.2.3. Self-efficacy

The patients' self-efficacy levels were evaluated using the Chinese Self-Efficacy Scale (C-SUPPH) for Cancer Patients. Qian et al. translated and adapted the C-SUPPH using the scale developed by Lev et al. as a refer.^11–12There were a total of 28 items, spread across three dimensions. A five-point Likert scale was utilized to assess the responses, with 1 indicated low confidence and 5 indicated high confidence.In the C-SUPPH scale, which had a point range of 28 to 140, higher scores indicated greater levels of self-efficacy.The Cronbach's alpha for the C-SUPPH was 0.97.

2.2.4. Social support

The patients' level of social support was assessed using the Social Support Rating Scale (SSRS) developed by Xiao et al.¹³It consisted of 10 items on three subscales: subjective support, objective support,and utilization of support.The SSRS was scored on a scale of 11 to 60, with a higher score indicating greater social support. The Cronbach's alpha for the SSRS was 0.86.

2.3.Data collection

Participants in the survey were given a paper questionnaire between October 2022 and May 2023.The two survey administrators received ongoing training to ensure that they fully understood the purpose and significance of every question in the questionnaire.Prior to completing the questionnaire, each participant was required to sign an informed consent form. The responders returned the questionnaire promptly after filling it out individually. The questionnaires were then examined by two investigators, who had to identify and cross out any that contained logical contradictions or missing items. The guideline of having 5–10 individuals for each item on the questionnaire was used to calculate the sample size. Considering that 20% of questionnaires were invalid, a minimum of 132 participants was required. The study involved distributing 240 questionnaires, of which 225 were considered valid and returned, resulting in a 93.75% recovery rate.

2.4. Statistical analysis

The statistical analysis program SPSS version 26.0 (IBM, CHINA) was utilized for data entry and examination.The data was double reviewed by two research assistants.Normality tests were performed to determine if the data fit into a normal distribution.Percentages and frequencies were used to describe the count data, while means ± standard deviations were used to describe the measurement data.Patients with different characteristics of esophageal cancer undergoing radiotherapy were compared using the T-test and analysis of variance.The relationship between the variables was examined using Pearson correlation analysis.Finally,we examined the factors influencing cancer-related fatigue in patients undergoing radiation therapy for esophageal cancer using multiple linear regression analysis.The SPSS PROCESS 3.3 plug-in was utilized to determine the significance of mediating effects. The significance level for all statistical tests was set at 0.05.

2.5. Ethical considerations

The study was approved by the University and Hospital Ethics Committee (2022-SR-741)and complied with the ethical requirements of the Helsinki Declaration.The patients’ rights to privacy and informed consent were fully respected and protected throughout the study, and they were informed that they had the freedom to stop participating in the study at any time.

3.1.Univariate analysis of CRF in esophageal cancer patients

There was a statistically significant difference (P < 0.05) in the cancer-related fatigue scores based on age, employment status, financial income, type of health insurance, number of radiotherapy treatments, duration of disease, tumor stage, degree of swallowing function obstruction, sleep status, and comorbidity with chronic diseases. The results are displayed in Table 1.

Table 1 Characteristics of patients with esophageal cancer (N=225)

Variable	n（%）	`X±s	t/F	P
Participants
Age (years)			15.770	＜0.001
＜60	46（20.4）	34.57±3.34
60-70	102（45.3）	34.86±4.09
＞70	77（34.2）	40±7.70
employment status			4.560	0.011
In-service	12（5.3）	33.75±2.45
retired	87（38.7）	34.60±4.89
unemployed	126（56.0）	38.18±6.45
Monthly household income			3.506	0.016
＜1000	35（15.6）	45.40±4.36
1000-3000	127（56.4）	35.80±4.61
3000-5000	45（20.0）	33.69±4.38
＞5000	18（8.0）	31.89±4.52
Type of medical insurance			8.473	＜0.001
Self-financed	2（0.9）	55±0
Resident Medical Insurance	136（60.4）	37.78±5.94
Employee Medical Insurance	85（37.8）	34.49±4.50
Commercial Medical Insurance	2（0.9）	23±1.41
Number of radiation treatments			9.521	＜0.001
＜10	114（50.7）	35.15±5.67
10-20	67（29.8）	37.61±5.60
＞20	44（19.6）	38.61±6.65
Duration of illness			10.891	＜0.001
＜1	186（82.7）	34.49±3.85
1-3	30（13.3）	44.60±3.06
＞3	9（4.0）	52.56±2.01
Tumor stage			6.223	＜0.001
Stage I	2（0.9）	23±1.41
Stage II	77（33.8）	31.87±2.72
Stage III	98（43.0）	36.33±2.90
Stage Ⅳ	48（21.1）	45.13±4.87
Degree of swallowing function obstruction			6.747	＜0.001
No obstruction	4（1.8）	26.75±3.40
Mild obstruction	100（44.4）	34.02±4.70
Moderate obstruction	114（50.7）	38.11±4.80
Severe obstruction	7（3.1）	53.29±1.60
Sleep quality			9.188	0.003
better	87（38.7）	33.26±3.66
mediocre	138（61.3）	38.64±6.27
Comorbidity with chronic diseases			18.728	＜0.001
yes	145（64.4）	39.41±5.43
no	80（35.6）	31.39±2.52

3.2.Correlation analysis of CRF with social support and self-efficacy in patients undergoing radiotherapy for esophageal cancer

The total cancer-related fatigue score was negatively correlated with social support and self-efficacy scores in esophageal cancer radiotherapy patients (r=-0.936**, P<0.05; r=-0.948**, P<0.05). The results are displayed in Table 2.

Table 2 Correlation analysis of CRF with social support and self-efficacy in patients undergoing radiotherapy for esophageal cancer (N = 225, r)

variables	physical fatigue	cognitive fatigue	emotional fatigue	Total score for cancer-related fatigue
social support	-0.794**	-0.164*	-0.473**	-0.936**
self-efficacy	-0.801**	-0.212**	-0.436**	-0.948**

Note: **p < 0.05, **p < 0.05, r:correlation coefficient

3.3.Multiple linear regression analysis of CRF in radiotherapy patients with esophageal cancer

Multiple linear regression analyses were performed using stepwise regression with CRF as the dependent variable. Statistically significant variables from both one-way and correlation analyses were utilized as the independent variables.The results are displayed in Table 3.

Table 3 Results for multiple linear regression analysis of CRF in patients treated with radiotherapy for esophageal cancer (N=225)

variables	β	SE	β´	t	p
constant term (math)	49.199	1.569		31.362
self-efficacy	-0.126	0.017	-0.350	-7.378	＜0.001
social support	-0.165	0.031	-0.269	-5.235	＜0.001
Tumor stage	0.743	0.187	0.094	3.981	＜0.001
Duration of illness	2.968	0.232	0.247	12.789	＜0.001
Degree of swallowing function obstruction	0.710	0.165	0.070	4.315	＜0.001
Number of radiation treatments	-0.227	0.111	-0.029	-2.050	0.042

Note: R² = 0.960, adjusted R² = 0.959, F = 751.181, p < 0.001. β: regression coefficient, SE: standard error of the regression coefficient,β´: standard regression coefficient.

3.4.Relationship analysis of social support, self-efficacy,and CRF in patients undergoing radiotherapy for esophageal cancer

The mediating effect analysis was performed based on the regression analysis results using the Process plug-in, with CRF as the dependent variable, self-efficacy is the independent variable, while social support serves as the mediating variable,and variables that were statistically significant in multiple linear regression analysis as the control variables.According to the findings, social support partially moderated the relationship between self-efficacy and CRF (β = -0.342, P < 0.01). The intermediate influence of -0.342 accounted for 36.08% of the total impact of -0.948.The interaction effects between variables are shown in Table 4.

Table 4 Analysis of the mediating effect of social support on the effect of self-efficacy on CRF (N=225)

Type of effect	efficiency value	SE	relative effect（%）
total effect	-0.948	0.008	100
direct effect	-0.606	0.023	63.92
indirect effect	-0.342	0.012	36.08

4.1.High incidence of CRF in patients treated with radiotherapy for esophageal cancer

The total score for CRF in patients undergoing radiotherapy for esophageal cancer in the present study was (27.78 ± 7.26), and 86.7% of patients were moderately or severely fatigued, indicating that CRF was high, which agrees with the findings of previous studies.^14,15Several factors may explain these outcomes:① The tumor itself and radiation therapy cause a variety of symptom clusters, which are exacerbated over time, seriously affecting the patients' physical and emotional well-being and making them susceptible to the symptoms of fatigue.②Abnormal release of inflammatory factors from the tumors leads to elevated interleukin-6 expression.Studies have shown that increased interleukin-6 level is significantly associated with fatigue, pain, and sleep disturbance.¹⁶③Esophageal cancer patients are typically middle-aged and elderly individuals. Some studies have shown that the function of the body declines with age. In the case of cancer, CRF is more likely to occur in the elderly patients.¹⁷Given this, medical personnel should be mindful of evaluating and managing symptom clusters in patients undergoing radiotherapy for esophageal cancer, formulate reasonable management strategies to reduce patients' symptomatic distress, satisfy their supportive care needs, reduce the occurrence and advancement of CRF and improve the quality of life for patients, especially older patients.

4.2. Analysis of factors influencing CRF in patients treated with radiotherapy for esophageal cancer

4.2.1. Tumor stage

According to the findings of the current study, patients undergoing radiation therapy for esophageal cancer had an increased risk of developing CRF based on their tumor stage.Some studies have shown that the tumor stage in cancer patients represents disease severity.¹⁸ On one hand, patients with a higher tumor stage are more prone to CRF due to rapid disease progression, poorer physical and mental condition, and worse prognosis. On the other hand, the higher the tumor stage, the higher the dose required for treatment, and the adverse effects induced by radiotherapy can further exacerbate the symptoms of fatigue. According to another study, tumor stage independently influences the survival of patients with esophageal cancer.¹⁹Therefore, medical personnel should pay particular attention to patients with high tumor stages, identify potential symptomatic distress in a timely manner, provide targeted guidance, and give psychological relief to alleviate CRF.

4.2.2 .Duration of illness

This study shown that individuals with esophageal cancer experience increasing levels of CRF over time.CRF in patients tends to rise dynamically as the tumor develops and as treatment progresses. In addition, with the prolonged course of the disease, the high medical expenses become a considerable financial burden to the patients, increase their physical and mental challenges, and aggravate CRF. Other researchers have also verified that financial stress related to cancer is closely associated with an elevated risk of negative physical and psychological consequences.²⁰In the future, reasonable and effective social support should be provided to the patients experiencing long-term disease. Government policies and health insurance systems should aim to reduce the subjective and objective patient burdens and alleviate CRF.

4.2.3 .Degree of swallowing function obstruction

The degree of swallowing function obstruction was an influential factor in CRF in patients receiving radiotherapy for esophageal cancer in the present study. To some extent, the degree of dysphagia is represented by the obstruction of the swallowing function. Due to the special anatomical location of the esophagus, patients with severe dysphagia face problems, such as inability to eat or pain during eating, which seriously affect their nutritional status and quality of life. One study demonstrated a correlation between dysphagia symptoms in esophageal cancer patients and their quality of life.²¹This suggests that healthcare professionals should promptly implement measures to promote swallowing function training in order to improve patients' swallowing and eating abilities.Furthermore, a specialized nutritional management program should be established for patients suffering from dysphagia caused by esophageal cancer. Considering the degree of obstruction, enteral or parenteral nutritional support should be promptly provided to improve the patients' nutritional status and alleviate CRF.

4.2.4 .Number of radiation treatments

The number of radiotherapy sessions was an influential factor in CRF in patients undergoing radiotherapy for esophageal cancer. It is possible that radiation therapy produces a series of toxic side effects while killing regional tumor cells, exacerbating the patient's symptoms of fatigue. According to a specific study, individuals with esophageal cancer experience fatigue symptoms throughout their radiotherapy treatment, and these symptoms worsen as the number of radiotherapy sessions increases.⁴Therefore, healthcare professionals should provide more physical and mental support to patients undergoing a significant number of radiotherapy sessions, guide them to actively cope with the adverse reactions brought by radiotherapy, promptly address negative emotions, and alleviate CRF .

4.3.Analysis of the correlation between social support, self-efficacy, and cancer-related fatigue in radiotherapy patients with esophageal cancer

According to the findings of the current study, CRF was found to have a negative association with both social support and self-efficacy in patients undergoing radiation therapy for esophageal cancer. In other words, the more severe the CRF, the lower the patient's levels of these two variables.Studies have shown that patients' fatigue levels can be reduced through social support,^22,23Effective social support can reduce patients' negative emotions, improve disease coping ability and treatment adherence, and relieve symptomatic distress. A crucial aspect of self-management, self-efficacy helps patients improve their lives by enhancing their physical and emotional health.Research indicates that individuals with higher levels of self-efficacy demonstrate better self-management skills and are more capable of managing the unpleasant emotions and harmful side effects associated with their condition.²⁴The current study's findings are consistent with a study conducted by Deng et al.²⁵which confirmed that nursing interventions grounded in the self-efficacy theory can reduce CRF in postoperative esophageal cancer patients.Therefore, healthcare professionals should fully recognize the value of social support and self-efficacy and provide adequate social support to patients undergoing radiotherapy for esophageal cancer to improve their self-efficacy and alleviate their fatigue level.

4.4.Relationship analysis of the effects of social support and self-efficacy on cancer-related fatigue in patients undergoing radiotherapy for esophageal cancer

The current study has shown that among patients undergoing radiation therapy for esophageal cancer, social support serves as a mediating factor between self-efficacy and CRF .Social support directly predicted cancer-related fatigue and indirectly predicted it through self-efficacy. The social buffering hypothesis theory states that effective social support can alleviate patients' negative emotions and enhance their self-efficacy.²⁶The theory of unpleasant symptoms proposes that patients' responses to symptom distress come from three main sources: physical, psychological, and social influences.⁶It also states that unmet supportive needs make patients feel lower levels of self-efficacy, which in turn increases symptom distress. Therefore, based on the theory of unpleasant symptoms, healthcare professionals can fully mobilize patients' social support systems by analyzing their psychosocial factors, enhance patients' self-efficacy, strengthen their confidence in self-management, alleviate their physical and mental distress, and reduce CRF .

4.5. Limitations

The present study had several limitations. First, the cross-sectional design of the study made it impossible to infer a causal association between cancer-related fatigue, self-efficacy,and social support. For this reason, a design for longitudinal study is required to investigate the reciprocal relationships between cancer-related fatigue and other factors. Secondly, there was a possibility of reporting bias because all of the surveys relied on self-reported data. Third, Since the participants were selected from a single Chinese hospital, there might be a selection bias.Therefore, patients with esophageal cancer should be recruited for future research studies from different hospitals and regions.

This study examined the variables that affect CRF in patients undergoing radiotherapy for esophageal cancer.The theory of unpleasant symptoms forms the foundation for analyzing the pathways through which psychosocial variables impact CRF.As a result, it was recommended that healthcare professionals pay close attention to the social support provided for esophageal cancer patients in clinical practice to improve their self-efficacy and reduce fatigue. However, the study was conducted at only one hospital and had a small sample, introducing a risk of bias. Future multicenter and large-sample studies should incorporate more relevant variables, search for other possible mechanisms of action, and design longitudinal and experimental methods to justify the results of the present investigation.

Author Contribution

Yuqing Wang(First Author): Conceptualization, Methodology, Software, Investigation， Data Curation，Formal Analysis, Writing - Original Draft; Xunhan Sun: Investigation，Data Curation，Data Analysis;Xinyu Lu: Data Analysis，Supervision; Shuyu Zhang: Data Analysis，Supervision; Jianchun Xia (Corresponding Author): Funding Acquisition, Resources, Supervision, Writing - Review & Editing;Yuxi Zhang (Corresponding Author): Funding Acquisition, Resources, Supervision, Writing - Review & Editing.

Acknowledgements

The authors sincerely acknowledge the financial support from National Natural Science Foundation of China (71704084), Key Project on Elderly Health in Jiangsu Province (LKZ2022002), Clinical Capacity Improvement Project of Jiangsu Province Hospital (JSPH-NA-2021-1) and Postgraduate Research and Practice Innovation Program of Jiangsu Province, China (SJCX23-0828).The authors also give sincere thanks to all the patients undergoing radiotherapy for esophageal cancer for participating in our research.

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You are reading this latest preprint version

Factors influencing cancer-related fatigue in patients with esophageal cancer undergoing radiotherapy:pathway analysis

Status:

Version 1

Abstract

Background

Objective

Methods

Results

Conclusion

1. Introduction

2. Methods

2.1. Study and sample

2.2. Assessment instruments

2.2.1. Demographic characteristics

2.2.2. Cancer-related fatigue

2.2.3. Self-efficacy

2.2.4. Social support

2.3.Data collection

2.4. Statistical analysis

2.5. Ethical considerations

3. Results

4. Discussion

4.1.High incidence of CRF in patients treated with radiotherapy for esophageal cancer

4.2. Analysis of factors influencing CRF in patients treated with radiotherapy for esophageal cancer

4.2.1. Tumor stage

4.2.2 .Duration of illness

4.2.3 .Degree of swallowing function obstruction

4.2.4 .Number of radiation treatments

4.5. Limitations

5. Conclusions

Declarations

Author Contribution

Acknowledgements

References

Additional Declarations

Status:

Version 1