The core symptom in gastric cancer patients undergoing chemotherapy: a network analysis

doi:10.21203/rs.3.rs-3230355/v1

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Research Article

The core symptom in gastric cancer patients undergoing chemotherapy: a network analysis

https://doi.org/10.21203/rs.3.rs-3230355/v1

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Background

During chemotherapy for gastric cancer, patients may experience symptoms associated with both the disease and chemotherapy. There have been limited studies exploring the relationship between these symptoms. Network analysis can identify the core symptoms in the symptom network.

Objective

The purpose of this research was to investigate the core symptoms and contributing factors in gastric cancer patients undergoing chemotherapy.

Methods

A cross-sectional study of convenient samples of patients with gastric cancer undergoing chemotherapy was conducted. A total of 616 gastric cancer patients undergoing chemotherapy were enrolled between January 2021 and November 2022. The symptom network and node characteristics were analyzed using network analysis, and the factors affecting the symptom network were investigated using multivariate linear regression analysis.

Results

The findings indicated that 89% of gastric cancer patients undergoing chemotherapy experienced lack of appetite. Taste alteration was the most prominent symptom in the network analysis, with the strongest correlation between taste alteration and lack of appetite in patients. Multiple linear regression analysis showed that gender, history of tobacco use and chemotherapy cycles were the factors affecting taste alteration.

Conclusion

Taste alteration was the core symptom in gastric cancer patients undergoing chemotherapy. Interventions are likely to be most effective if symptom management focuses on taste alteration. Additionally, lack of appetite should be treated together in a clinical setting to ensure accurate symptom management.

Gastric cancer

chemotherapy

core symptoms

network analysis

taste alteration

According to the findings of this study, chemotherapy patients with gastric cancer report a variety of side effects. One modern approach to investigate and explain the links between symptoms is network analysis. This research seeks to identify core symptoms in people with gastric cancer and to provide theoretical support for precise symptom management in gastric cancer people undergoing chemotherapy.

According to the GLOBOCAN 2021 report published by the International Agency for Research on Cancer, there were an estimated 1.089 million incidence cases of gastric cancer worldwide and 769,000 deaths. Notably, China accounted for a substantial proportion, with 43.9% of reported cases and 48.6% of recorded deaths.¹ Chemotherapy is one of the most important means of anti-tumor therapy for gastric cancer patients and can be administered alone or in combination with other therapeutic modalities such as surgery.² However, while effectively targeting tumor cells, chemotherapy drugs also cause damage to normal cell structures and cause a wide range of toxic side effects.³ Patients receiving chemotherapy exhibited more complex symptoms than those not receiving this treatment, necessitating the management of both disease-related symptoms and various treatment-induced adverse events.

Some studies have found that symptoms cluster change over time during chemotherapy,^4,5 but core symptoms can be stable in symptom groups and closely related to each symptom. Therefore, core symptoms are considered to be the key to synergistic enhancement among symptoms and can be used to develop effective symptom management measures. Most research has focused on patients' symptoms; However, few studies have explored correlations between symptoms. Identifying central symptoms, which are comprised of symptoms, makes sense as it can help to understand the underlying mechanisms of symptom experience and identify targets for effective symptom management. To manage groups of symptoms, interventions that target their underlying mechanisms are considered more cost-effective than those that target individual symptoms.⁶

Network analysis can effectively explore the correlation between symptoms and is a novel approach to explore and interpret the relationship between symptoms.⁷ It enables us to visualize the internal network structure of symptoms in patients with gastric cancer undergoing chemotherapy, which can not only help researchers identify the severity of symptoms but also explore the density, intensity, intimacy, intermediacy, and other mechanical indicators of symptoms. Network analysis can identify the core symptoms, those that are most influential and reinforcing in the symptom network. That is, core symptoms are most strongly correlated with other symptoms.⁸ Understanding core symptoms has potential benefits in understanding the mechanisms of disease occurrence and maintenance.⁹ Interventions need to focus on the core symptoms using biological or psychosocial approaches to treat them as effectively as possible, as this can cause a domino effect of other related symptoms.¹⁰ Researchers believe that network analysis has the potential to realize precision medicine for cancer patients.¹¹ Therefore, the identification of core symptoms is important to achieve accurate symptom management in gastric cancer patients undergoing chemotherapy.

At present, network analysis is mainly used in mental and psychological disorders,¹² behavioral¹³ and sociological.¹⁴ Few studies have reported using network analysis to manage symptoms in cancer patients.¹⁵ According to a study examining core symptoms in multiple myeloma patients undergoing chemotherapy, pain was the most prevalent, worry was the most dominant, and nausea and vomiting were the strongest correlations.¹⁵ In another study, a network analysis of psychological symptoms in head and neck cancer patients undergoing intensity-modulated radiotherapy revealed that depression was at the core of the network, with female gender, higher levels of stress, and a history of alcohol use as influencing factors.¹⁶ In a study by Papachristou et al.,¹⁷ nausea was identified as the most central symptom in cancer chemotherapy patients, with the greatest centrality index, i.e. intensity, indicating that nausea was most strongly correlated with other symptoms within the network. However, no study has explored the core symptoms of gastric cancer patients undergoing chemotherapy.

Therefore, the aim of this study was to identify the core symptoms of gastric cancer patients undergoing chemotherapy and analyze their influencing elements to provide theoretical support for precise symptom management in gastric cancer patients undergoing chemotherapy.

Patients and Settings

The multicenter, cross-sectional study was designed to identify core symptoms in stomach cancer patients undergoing chemotherapy. A total of 616 patients were recruited from four hospitals (the Affiliated Hospital of Nanjing University of Chinese Medicine, the Wuxi Hospital of Chinese Medicine, the Suzhou Hospital of Chinese Medicine, and the Xuzhou Hospital of Chinese Medicine). The inclusion criteria were as follows: 1) Patients diagnosed with gastric cancer; 2) Receive postoperative chemotherapy, 3) Age ≥ 18 years, 4) Informed of the condition and agreeing to participate in the study. The exclusion criteria are as follows: 1) Combined with serious heart, brain, kidney, and other functional disorders, 2) Suffering from severe cognitive dysfunction or mental illness.

Instruments

Demographic and Clinical Characteristics.

The questionnaire was designed to capture demographic and clinical characteristics, including age, gender, marital status, medical payment, education level, history of alcohol use, history of tobacco use, history of car sickness, cancer stage, the chemotherapy cycles, and chemotherapy regimen.

MD Anderson Symptom Inventory Gastrointestinal Cancer (MDASI-GI)

The MD Anderson Symptom Inventory (MDASI) is a self-assessment scale that was created by the University of Texas M. D. Anderson Cancer Center in 2000 to to assess the impact of 13 common cancer symptoms patients had in the past 24 hours on six aspects of daily life.¹⁸ In this study, we used the first part of the scale. The MDASI was translated into Chinese by Wang et al. (2004),¹⁹ who reported an internal consistency Cronbach's α of 0.87. To assess gastrointestinal cancer symptoms, Wang et al. (2010) developed the MDASI gastrointestinal cancer module, which comprises 18 items, including the original 13 symptoms and five gastric-cancer-specific symptoms (pain, fatigue, nausea, sleep disturbance, distress, shortness of breath, difficulty remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting and numbness, constipation, diarrhea, difficulty swallowing, taste alteration, and feeling bloated).²⁰ The module demonstrated good internal consistency with a Cronbach's α coefficient of 0.80 and used an 11-point Likert scale with a range of 0–10 for each item, where a higher score reflects greater symptom severity.

Procedures

This study was approved by the Institutional Review Board of the Affiliated Hospital of Nanjing University of Chinese Medicine (protocol number: 2021NL-089-03). Data collection took place on the second day of chemotherapy for the patients and, after obtaining consent, participants were informed of the methodology for completing an electronic questionnaire. Participants completed general demographic information and the MDASI-GI electronic questionnaire on the Hospital Research Data Acquisition and Management System platform. Following the release of data from the hospital system, we meticulously reviewed and eliminated questionnaires that contained incomplete information. A questionnaire is deemed invalid if more than 10 per cent of its items are left unanswered.

Statistical Analysis

Sample size estimation

In this study, we investigated a total of 18 symptoms in patients. The sample size for the network analysis is estimated at 153,²¹ and considering the attrition rate of 10–15%, the calculated sample size is at least 169 cases. Our actual sample size is larger than the calculated sample size.

Network analysis

The statistical analyses were performed using R version 4.2.1 and the qgraph package. The symptom network diagram was constructed using EBICglasso and Spearman's correlation analysis, where each node represented a symptom and the edges represented relationships between symptoms. The thickness of the edges indicated the strength of correlation between two symptoms.

Node centrality

Node centrality serves as a mechanistic indicator for identifying core symptoms. We conducted centrality analysis using three metrics (Strength, Betweenness, and Closeness).²² Strength measures node significance by calculating the sum of absolute correlation coefficient weights of edges. The greater the value, the stronger the influence of a symptom on other symptoms and its higher importance.²³ Closeness measures a node's distance from other nodes by calculating the reciprocal of its distance from other nodes. A larger closeness value indicates that a symptom is closer to other symptoms and more likely to be in the center of the network. The Betweenness indicator can be utilized to evaluate the probability of a node functioning as a bridge within the network, and it can be quantified by enumerating the frequency at which a node lies on the shortest path connecting any two other nodes. A higher count signifies an increased likelihood that the symptom is indicative of bridging. The stability and accuracy of estimated networks serve as two indicators reflecting the robustness and precision of the estimations. Stability was assessed by computing the correlation stability coefficient, with a recommended threshold of at least 0.25, while a coefficient exceeding 0.50 is considered indicative of high stability.¹⁷ The 95% confidence intervals (CIs) for edge weight values were calculated in order to assess the accuracy of the estimated network connections.²⁴

Influencing factors of core symptoms

SPSS version 25.0 was used to analyze the data (IBM Co., Armonk, NY, USA). To descript continuous variables that have a normal distribution, mean scores with standard deviation were used. According to the characteristics of the data, analysis of the difference test in this study primarily utilized the T-test and analysis of variance. Furthermore, the independent variables were substituted into the multiple linear regression equation for the regression test. Additionally, the variance inflation factor (VIF) and tolerance tests were applied to assess the possibility of multicollinearity. All analyses were double-tailed, and P < 0.05 was used to denote statistical significance.

Characteristics of participants

This study included a total of 616 patients diagnosed with gastric cancer, Overall, participants were aged (mean age 61.45 ± 10.58), mostly male (72.6%). The vast majority were married (99.1%) and medical insurance was the primary source of payment for medical expenses (93.5%). Furthermore, oxaliplatin chemotherapy was administered to the majority of patients (67.4%). Specific details are presented in Table 1.

Table 1

༎General demographic of gastric cancer patients (n = 616)
Variable	Categories	() / n (%)
Age		61.45 ± 10.58
Gender
	Male	447 (72.56%)
	Female	169 (27.44%)
Marital status
	Married	610 (99.03%)
	Single	6 (0.01%)
Medical payment
	Medical insurance	576 (93.51%)
	Self-paid	40 (6.49%)
Education level
	Elementary	211 (34.25%)
	Junior high	191 (31.01%)
	Senior high	150 (24.35%)
	College or above	64 (10.39%)
History of alcohol use
	No	469 (76.14%)
	Yes	167 (27.11%)
History of tobacco use
	No	414 (67.21%)
	Yes	202 (32.79%)
History of car sickness
	No	571 (92.69%)
	Yes	45 (7.31%)
Cancer stage
	Ⅰ	47 (7.62%)
	Ⅱ	152 (24.68%)
	Ⅲ	313 (50.81%)
	Ⅳ	104 (16.88%)
Chemotherapy cycles
	≤3	451 (73.21%)
	3–6	110 (17.86%)
	>6	55 (8.93%)
Chemotherapy regimen
	Oxaliplatin	415 (67.4%)
	Cisplatin	21 (3.41%)
	Fluorouracil	219 (35.6%)
	Paclitaxel	111 (18.0%)

Symptom prevalence and severity

In terms of symptom prevalence, lack of appetite was the most frequently reported symptom (n = 551, 89.45%), followed by fatigue (n = 542, 87.99%), taste alteration (n = 517, 83.93%), distress (n = 491, 79.71%), and sleep disturbance (n = 475, 77.11%). With respect to symptom severity, lack of appetite was rated as the most severe symptom (3.08 ± 2.14), followed by fatigue (3.01 ± 2.00), taste alteration (2.63 ± 2.00), distress (2.62 ± 2.04), and sleep disturbance (2.51 ± 2.24). Details are shown in Table 2.

Table 2

༎Symptom prevalence and severity of participants (n = 616)
symptoms	n (%)	()
Pain	364 (59.09)	1.72 ± 1.99
Fatigue	542 (87.99)	3.01 ± 2.00
Nausea	450 (73.05)	2.32 ± 2.10
Sleep disturbed	475 (77.11)	2.51 ± 2.24
Distress	491 (79.71)	2.62 ± 2.04
Shortness of breath	206 (33.44)	0.82 ± 1.48
Difficulty remembering	378 (61.36)	1.52 ± 1.61
Lack of appetite	551 (89.45)	3.08 ± 2.14
Drowsiness	280 (45.45)	1.35 ± 1.85
Dry mouth	399 (64.77)	1.77 ± 1.82
Sadness	451 (73.21)	2.10 ± 1.98
Vomiting	374 (60.71)	1.92 ± 2.24
Numbness	290 (47.08)	1.30 ± 1.83
Constipation	261 (42.37)	1.26 ± 1.88
Diarrhea	237 (38.47)	1.07 ± 1.73
Difficulty swallowing	173 (28.10)	0.77 ± 1.56
Taste alteration	517 (83.93)	2.63 ± 2.00
Feeling bloated	440 (71.43)	2.05 ± 1.91

Network analysis and centrality indices

Based on the thickness of the edges in the symptom network, the top three symptom pairs with strong correlation between symptoms are: Taste alteration-lack of appetite (r = 0.80); Nausea-Vomiting (r = 0.76); Sadness-Distress (r = 0.75) (Fig. 1). According to the centrality index, the highest strength centrality index was taste alteration (r_s=1.49), followed by sadness (r_s=1.25) and vomiting (r_s=0.74). The highest closeness centrality index was taste alteration (r_c=1.75), followed by sadness (r_c=1.05) and feeling bloated (r_c=1.04). The highest betweenness centrality index was taste alteration (r_B=3.20), followed by fatigue (r_B=1.49), feeling bloated (r_B=1.48) (Fig. 2) .

Accuracy and stability of symptom networks

The bootstrapped CIs were tiny, which demonstrated the extreme accuracy of the network. After testing, the correlation stability coefficient of the symptom network was found to be greater than 0.5 for both strength and closeness, indicating that the network remained stable. (Fig. 3). After dropping up to 75% of the sample, the order of symptoms in intensity remained correlated with the original network.(r = 0.76) (Fig. 4). Therefore, we concentrated on the interpretation of symptom strength based on this network analysis.

Influencing factors of taste alteration

The results of univariate analysis showed that there were statistically significant differences in taste alteration among different genders, history of tobacco use and chemotherapy cycle (P < 0.05) (Table 3). In contrast, no significant differences were found between the following influences: age, marital status, medical payment, education level, history of alcohol use, history of car sickness, cancer stage and chemotherapy regimen (P > 0.05). The collinearity diagnosis resulted in tolerance values ranging from 0.851 to 0.993 and VIF values ranging from 1.007 to 1.175, indicating that there was no multicollinearity in these variables and that a multivariate linear regression analysis could be performed. Furthermore, the results of multiple regression analysis showed that history of tobacco use, gender and chemotherapy cycle were the influencing factors (P < 0.05). (Table 4)

Table 3.

Factors related to taste alteration among participants (n = 616)
Variable	F/t	p
Age	1.327	0.067
Gender	2.881	0.012
Male
Female
Marital status	0.725	0.439
Married
Single
Medical payment	0.067	0.503
Medical insurance
Self-paid
Education level	0.738	0.996
Elementary
Junior high
Senior high
College or above
History of alcohol use	0.041	0.076
No
Yes
History of tobacco use	12.237	0.004
No
Yes
History of car sickness	4.442	0.291
No
Yes
Cancer stage	2.923	0.119
Ⅰ
Ⅱ
Ⅲ
Ⅳ
Chemotherapy cycles	2.323	0.002
≤ 3
3–6
>6
Chemotherapy regimen
Oxaliplatin	0.095	0.405
Cisplatin	0.005	0.126
Fluorouracil	1.532	0.070
Paclitaxel	0.644	0.562

Table 4

Multiple linear regression analysis of taste alteration (n = 616)
						Collinearity statistics
	B	S.E	Beta	T	P	Tolerance	VIF
Constant	0.728	0.376	-	1.937	0.053	-	-
Gender	0.460	0.178	0.103	2.580	0.010	0.851	1.175
History of tobacco use	0.544	0.169	0.128	3.220	0.001	0.989	1.011
Chemotherapy cycles	0.437	0.124	0.140	3.525	< 0.001	0.993	1.007
R² = 0.046; adjusted R² = 0.041; F = 9.763, p < 0.001. VIF variance inflation factor; B unstandardized coefficients; S.E. standard error; β standardized coefficients

This study was the first to examine core symptoms in gastric cancer patients undergoing chemotherapy and to assess demographic and clinical characteristics of patients associated with the symptom network. Network analysis increased our understanding of how symptoms relate to each other and identifies core symptoms and features associated with symptom networks.

In terms of symptom prevalence, lack of appetite was the most frequently reported symptom (n = 551, 89.45%). Concerning symptom severity, lack of appetite was also rated as the most severe symptom (3.08 ± 2.14). The results of this study was inconsistent with the conclusion of Henry et al.,²⁵ who showed that fatigue was a a bridging symptom, which may be related to the heterogeneity of the study objects, the method of constructing the network model, and the different evaluation time points. In addition, lack of appetite, nausea, and vomiting constitute gastrointestinal symptoms in cancer patients during treatment.²⁶ Given the interaction of symptoms within symptom groups, nausea and vomiting can affect patients' appetite, reduce their intake of nutrients, and then affect their mental state and aggravate fatigue symptoms. Therefore, drugs^27,28 and acupressure can be used to prioritize intervention in patients' gastrointestinal symptoms, especially in appetite, to ensure patients' basic energy intake and better cope with the adverse effects of treatment.²⁹

According to the centrality index, the highest strength centrality index was taste alteration (r_s=1.49). The highest closeness centrality index was taste alteration (r_c =1.75). The highest betweenness centrality index was taste alteration (r_B=3.20). A total of 83.93 percent of participants experienced taste alteration. This prevalence rate was higher than that of previous studies.^30–31 Studies^32,33 had shown that most cancer patients who received chemotherapy experience a change in taste at the first chemotherapy treatment. Of these, about 59% of patients went into remission during the interval of chemotherapy and their symptoms reappeared during follow-up. In 35% of patients, the change in taste persisted, and patients often complained of "no taste" and "this taste cannot be described in words." Some chemotherapy patients even had abnormal tastes such as bitter and metallic taste without eating. For example, the proportion of metallic taste in the mouth accounts for 9.7–78%, which seriously affected the quality of life of patients. According to statistics, taste alteration made about 40% of tumor chemotherapy patients suffer from malnutrition, wasting, etc.^34,35 Taste alteration can cause not only physical problems, but also emotional distress, resulting in decreased appreciation of food, and negatively affecting social functioning. In severe cases, it can reduce patients' chemotherapy compliance and tolerance, resulting in poor clinical prognosis.

It had been reported that taste alteration may cause malnutrition in cancer patients, resulting in decreased appetite, aversion / dislike of certain foods, changes in food preferences, insufficient energy intake, or weight loss. Malnutrition is a condition that significantly affects the prognosis of cancer patients, including poor prognosis and treatment outcomes, decreased functional status and quality of life, toxicity from chemotherapy, and increased risk of postoperative complications.^36–38 Network analysis helps us identify central symptoms by providing information about the relationship between symptoms. Taste alteration was the core symptom of patients with gastric cancer undergoing chemotherapy and had the greatest impact on other symptoms. Previous studies had suggested that targeting core symptoms may be a more effective symptom intervention as it affected multiple co-existing symptoms.³⁹ Our findings informed the field of symptom clustering studies by testing a novel approach to identifying core symptoms. Therefore, it is suggested that when patients with gastric cancer undergoing chemotherapy have multiple symptoms at the same time, high-intensity and precise intervention on taste alteration can reduce the transmission effect of taste changes as an intermediary between symptoms in the symptom network, reduce the severity of other symptoms while reducing taste alteration, and further improve the accuracy and intervention efficiency of gastric cancer symptom management. Next, it is necessary to further study the core role of taste change in gastric cancer patients undergoing chemotherapy, explore the mechanisms of their association with other symptoms, and further enhance the intervention efficiency and precision of interventions for gastric cancer symptom management.

The symptom network was shown to be the thickness of the connections between the nodes and the edges, which accounted for the strength of the relationship. Our study found the top three symptom pairs with a strong correlation between symptoms are: Taste alteration-lack of appetite (r = 0.80); Nausea-Vomiting (r = 0.76); Sadness-Distress (r = 0.75). Studies by Cherwin et al.⁴⁰ found similar findings, with altered taste and loss of appetite being the most common gastrointestinal symptoms. The networks identified were comparable to those of Papachristou et al.,¹⁷ and Rha et al.³¹ The possible reason is that in addition to the stimulation of chemotropic cells on digestive mucosa to release 5-HTP and activate the receptor by chemotherapy drugs, the physiological response to the chemoreceptor of the vagus nerve and the vomiting center will cause gastrointestinal dysfunction, and the change of basic taste, abnormal taste, and overall taste will also cause appetite loss. In addition, patients need to eat a light diet, supplement high-quality protein to help the body recover, and change the original eating habits, which also aggravate the eating trouble.

According to our findings, reducing taste alteration could help alleviate other symptoms and maximize the effectiveness of the intervention. Interventions to alleviate altered taste are as follows: first, it is recommended that "use plastic tableware that meets national quality standards instead of metal tableware, or eat warm and cool food (except for patients using oxaliplatin chemotherapy) can greatly improve the taste of metal", and patients who are not sensitive to sweet and sour taste are recommended to push the food as far as possible to the soft palate, where taste buds are extremely rich. In addition, early screening and evaluation can prevent the development of its severity in the first place. Standardized and easy-to-use assessment methods, including patient self-report outcomes, are recommended for this symptom, which is necessary for the diagnosis and management of altered taste.^41,42 Nurses should pay attention to the appetite changes of chemotherapy patients, consider the diversified diet culture, combine the diet structure and habits of patients in different regions, and actively explore individualized intervention strategies to manage the eating behavior of patients. Therefore, while appropriate interventions are taken to alleviate the taste alteration, other symptoms will also be alleviated, maximizing the effect of the intervention.

According to Symptom Experience Mould (SEM),⁴³ individual and clinical characteristics have an impact on the symptom experience of patients with gastric cancer undergoing chemotherapy.⁴³ This study shows that gender, chemotherapy cycle, and history of tobacco use are factors affecting the core symptoms. The medical staff was able to concentrate on incorporating these factors incorporated into clinical management to improve symptom management in gastric cancer patients. The clinical implications of these impact factors are discussed in the following sections. In the present study, the score for taste alteration was higher in female patients than in male patients. The possible reason may be that women may have more myxoid taste buds and taste pores than men, resulting in higher taste sensitivity.^44,45 It is also possible that the psychological burden of the disease is heavier in women than in men, that anxiety and depression are more common in women, and that taste changes are closely related to anxiety and depression.⁴⁶ As for the history of tobacco use, smoking is reported to interfere with taste and smell, as the contents of tobacco may damage respiratory cells.^47,48 And smoking can worsen oral hygiene and even lead to oral diseases such as periodontitis, which limits patients' dietary intake. This increases the risk of malnutrition in patients.^49–52 For chemotherapy cycles, the taste alterations in patients with more than 6 cycles of chemotherapy may be due to CT-induced taste and odor alterations via cytotoxic damage to rapidly dividing taste and odour receptors.⁵³ Previous research has also demonstrated changes in taste over time in relation to treatment over time in relation to treatment.⁴² Our results suggest that follow-up of patients experiencing taste alteration is of critical importance in order to adjust strategies to manage taste alteration according to their changing characteristics. In summary, the sensitivity of core symptoms suggests that the aforementioned indicator features can be used to identify high-risk groups based on huge data and machine learning to build chemotherapy-related early warning models for gastric cancer patients for precise prevention and treatment to improve symptom burden. In contrast, no significant differences were found in age, marital status, educational level, drinking and car sickness history, cancer stage and chemotherapy regimen. Studies with larger sample sizes are needed to confirm or refute these findings.

Limitations

Some limitations should be taken into account in interpreting the current results. Firstly, this study used a cross-sectional design and we cannot explain the causal relationship between the different symptoms. Next, a similar longitudinal study design is warranted to further explore the sequence and causality of symptom onset. Secondly, since this study was self-reported, bias increased due to the lack of objective indicators. Thirdly, because the network analysis in this study was performed using cross-sectional measurements of symptoms from a single chemotherapy cycle, it remains unknown whether the identified symptom network remains stable or evolves over multiple chemotherapy cycles.

Implications for practice

Our study has important implications for symptom management in patients with gastric cancer undergoing chemotherapy. The core symptom is taste alteration. Nurses and health care teams should focus on the patient's core symptom to achieve the maximum effect of the intervention. In addition, of all the symptoms, the relationship between taste alteration and lack of appetite was the strongest. Nurses and medical teams should be managed together.

For patients with gastric cancer undergoing chemotherapy, the most common and painful symptom is taste alteration. The strongest correlation was between taste alteration and lack of appetite. Taste alteration is a core symptom. The frequency of chemotherapy, and motion sickness history were the influencing factors of taste alteration. By focusing on taste alteration while controlling symptoms in a clinical setting, interventions will have the greatest effect due to the chain reaction. Understanding the correlation between symptoms helps patients manage their symptoms. However, increasing sample sizes and using longitudinal studies in the future should allow better exploration of the relationship between different symptoms.

Acknowledgements

The authors’ special thanks go to all the gastric cancer patients who participated in this study. They also thank the medical oncology staff of the Affiliated Hospital of Nanjing University of Chinese Medicine, the Wuxi Hospital of Chinese Medicine, the Suzhou Hospital of Chinese Medicine, and the Xuzhou Hospital of Chinese Medicine.

Author contributions

Conceptualization: P.B.D., X.Q.W., Y.L.Z.

Data curation: P.B.D., X.Q.W., Y.L.Z., J.G., H.Y.G.

Formal analysis: P.B.D., X.Q.W., Y.L.Z, Y.L.

Methodology: P.B.D., X.Q.W., Y.L.Z, Y.L., X.L., Z.Y.Z.

Interpretation of Data: P.B.D., Y.L., X.L., Z.Y.Z., L.H.Y.

Writing-Original Draft: P.B.D.

Writing-Review and Editing: P.B.D., X.Q.W., Y.L.Z.

Funding This study was funded by the Jiangsu Traditional Chinese Medicine Bureau’s Scientifc Research Projects (no. ZD202005) , the Jiangsu Hospital of Traditional Chinese Medicine’s Special Project of Innovation and Development Fund (Y2021CX38) , the Jiangsu Hospital of Traditional Chinese Medicine’s Special Project of Nightingale Fund (Y23017).

Data availability The data will not be shared because the information of people with gastric cancer patients must be kept confidential.

Competing interests The authors declare no competing interests.

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No competing interests reported.

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The core symptom in gastric cancer patients undergoing chemotherapy: a network analysis

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Abstract

Background

Objective

Methods

Results

Conclusion

Figures

Key Message

Introduction

Methods

Patients and Settings

Instruments

MD Anderson Symptom Inventory Gastrointestinal Cancer (MDASI-GI)

Procedures

Statistical Analysis

Sample size estimation

Network analysis

Node centrality

Influencing factors of core symptoms

Results

Characteristics of participants

Symptom prevalence and severity

Network analysis and centrality indices

Accuracy and stability of symptom networks

Influencing factors of taste alteration

Discussion

Limitations

Implications for practice

Conclusion

Declarations

References

Additional Declarations

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