A qualitative study of the symptom management in patients with chemotherapy-induced hand-foot syndrome

doi:10.21203/rs.3.rs-3247627/v1

Purpose

To investigate the ability to self-manage symptoms in patients with chemotherapy-induced HFS and to provide guidance for developing a self-management plan that meets patient needs.

methods

From July 2022 to July 2023, 22 patients with chemotherapy-induced HFS were selected by objective sampling in the oncology department of a tertiary hospital in Shanghai. A semi-structured in-depth face-to-face interview was used to collect the case data, and the content analysis method was used for analysis, and the topic was refined.

Results

Twenty-two patients were interviewed. Three themes and six sub-themes emerged from the analytical interviews: the first theme was "Patient attitude and emotional response to symptoms," which consisted of patients gradually accepting the symptoms of HFS and adapting to some mild manifestations based on the following responses, showing different emotional responses to HFS, symptoms that affected their daily life. The patient feels guilty for his family and suffers from a self-image disorder. The second theme is "symptom experience," with symptoms that vary from patient to patient and have a different impact on the individual's life, including pain and itching. The third theme is "coping strategies," which include patients feeling the effects of limited social interaction and family relationships. The fourth topic, "Expectations for the future," includes gaining relevant knowledge through the website, doctors, and patients, changing habits, demonstrating symptom improvement, and meeting/exceeding the expectations of healthcare providers.

Conclusions

Healthcare providers should provide more education and emotional support to patients with chemotherapy-induced HFS to enable symptom management, elicit positive experiences.

Hand-foot syndrome

symptom management

tumor care

qualitative research

Hand-foot syndrome (HFS) or palmoplantar erythrocyte sensory disturbances are side effects associated with some systemic chemotherapies, particularly oral fluoropyrimidines such as capecitabine (Xeloda ®) [1, 2]. It causes redness and pain in the palms and/or soles of the feet [3]. Occasionally, thick calluses, blisters, or ulcers also appear, which makes it difficult to walk or use the hands. Furthermore, other opportunistic infections may lead to increased severity and complications [4, 5]. However, not all patients develop HFS, and the severity of symptoms may vary. Usually, HFS is not life-threatening and rarely requires hospitalization; however, it may cause significant discomfort and affect the patient's daily activities and quality of life [6, 7].

Although there are no standards for preventing HFS, there are recommendations for preventing and managing HFS through the use of specific medications based on expert opinion. The literature review also highlighted the importance of management based on accurate grading and patient education of HFS [8, 9]. Liang et al. [10] Skin toxicity distorts the daily activities of patients and negatively affects their self-image, social participation, and close relationships, according to the report. Another qualitative study[11] [12] It has also been shown that skin toxicity is associated with actual physical discomfort, appearance problems, social isolation, and high medical morbidity[13, 14].

HFS can be troublesome for patients, affecting their ability to carry out everyday activities and get on with their lives [15]. It is therefore important that healthcare professionals recognize and manage the symptoms and mitigate their impact [16]. This study utilizes qualitative research methods to conduct in-depth interviews with patients suffering from chemotherapy-induced HFS [17, 18], aiming to explore the balance between symptom self-management and seeking medical interventions [13, 19].

Study design

We conducted a qualitative study[20, 21], in which outpatients with advanced/recurrent cancer and chemotherapy-related HFS were interviewed individually [22-24]. This method is an inductive and descriptive method that helps to understand the complexity of human experience and has been widely used in the nursing field in recent years. This study was approved by the Ethics Committee of Ruijin Hospital. .All participants were informed in detail about the purpose of the study by the researchers, and all conversations would be recorded. Participants could withdraw from the study at any time. Each participant carefully read the informed consent form and signed the consent statement before the interview began[25].

Study participants and sampling strategy

An objective sampling method was used to select 22 patients with chemotherapy-induced HFS in the oncology department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from July 1 to September 30, 2022. The respondents’ data reached saturation and no new themes appeared. Patient experience was conveyed through individual semi‐structured interviews [23, 26]. The inclusion criteria were as follows: (I) had clinically confirmed mild, moderate, or severe HFS after chemotherapy, or grade 1 to 3 [1, 27], using the conventional toxicity determination criteria; (II) had clear thoughts and good language skills; and (III) voluntary participated in this study. The exclusion criteria were as follows: (I) patients with peripheral neuritis; (II) cervical disc herniation; or (III) psychiatric disorders. The principles of data saturation were applied [28]. Twenty-two patients (Ps) were eligible and completed the interview (Tables 1,2).

The research team interviewed that was designed based on previous phenomenological studies. We performed semistructured face-to-face in-depth interviews with the participants [29]. The questions are listed in Table 3. The interview was conducted and recorded in a quiet and separate room by the interview team. The study objective and confidentiality principles were explained and patient consent was obtained. During the interview, participants were encouraged to express their true thoughts. Changes in the respondents’ expressions were observed and recorded. The duration of the interview in this study was 20–40 min, with an average of 30 min per subject[30].

Data collection

The qualitative data were analyzed using the Colaizzi’s method [26]. Qualitative thematic analysis was used to code the interview transcripts and create categories of symptom management experience in patients with HFS [28, 31]. Data collection was conducted through post-appointment interviews with respondents. Audio recordings were transcribed within 24 hours of each interview; read the original data repeatedly; recall the interview situation; field record; the interview data were marked, saved, and backed up in detail.

Data analysis

Content analysis method was used to summarize and refine the topics. The specific steps were as follows: [31, 32]:

Stage 1: All interviews were recorded using audio equipment and transcribed within 24 hours;
Stage 2: Important statements about symptom management in patients with chemotherapy-induced hand-foot syndrome and views and experiences directly related to the patient were manually rereading, underlined, extracted, and numbered;
Stage 3: The implications of all important statements are summarized. In doing so, two PHDS with extensive experience in qualitative research reviewed their meaning composition;
Stage 4:The summarized meanings were grouped into thematic clusters. In this process, thematic clusters were compared with the raw data to determine consistency, and these processes were repeated several times;
Stage 5: Eleven subthemes were identified according to the research objectives and described in detail;
Stage 6: Similar subthemes were organized into larger clusters and four major themes were obtained;
Stage 7: The basic structure was returned to participants to verify that the content was consistent with their experience with symptom management.

In case of disagreement, consensus was reached through discussion. All participants agreed to be contacted again and provided their phone numbers to the researchers.

Rigour

Four criteria defined by Lincoln and Cuba were used to ensure methodological rigor: credibility, confirmability, reliability, and transferability [33, 34]. To increase confidence in the data, the final results were sent to all participants for confirmation and approval. Confirmability was ensured through a clear description of the study context, sampling, and data collection and analysis processes. For reliability, two external experts with experience in qualitative research reviewed the decision cues as well as the results and conclusions of the study [35]. In terms of transferability, the recruited respondents differed in a number of clinical and pathological factors, including age, sex, occupation, education level, work status, and tumor type and stage (Table 1). This report is guided by the Integrated Standards for Reporting Qualitative Research (COREQ) [23, 36, 37].

Baseline characteristics

The principles of data saturation were followed and the participants’ characteristics are detailed in Table 2. A total of 22 patients [9 females (40.91%); 13 males (59.09%)] were interviewed in this study. The participants were aged 34–73 years, with an average age of 58 years. In terms of primary cancer diagnosis, 9 (40.91%) had colon cancer, 7 (31.82%) had rectal cancer, and 6 (27.27%) had other cancers.

The interviewers were trained to conduct unified professional interviews using open-ended questions on the subject (16) (Table 3). Four thematic categories emerged from the analysis of the interview data: attitudes and emotional responses, symptom experience, social and family aspects, and experience in dealing with symptoms (Figure 1).

Attitude and emotional responses

Acceptance and adaptation

Our results suggested that the patients gradually accepted the symptoms of HFS and adapted to some mild manifestations based on the following responses [38]. The symptoms of HFS caused different psychological burdens to patients and they felt powerless to engage in daily activities [39].

“The hands and feet are sometimes numb for a long time, also, I am used to this feeling, also feel nothing, so I did not say.” (A7)

“I have had chemotherapy for more than 60 times, have been numb feeling, sometimes peeling for a long time.” (A1)

Anxiety and concern

Patients showed different emotional responses to the HFS, symptoms that affected their daily lives [27, 40].

“The impact is really not trivial, I am not able to do a lot of things that were used to be easy , for example, needing my family to help with washing hair. Cannot fall sleep at night also could not sleep well, this foot numb, a little rest is not good (shake his head)! Afraid that it will become increasingly serious in the future ah!” (A8)

“You see there are very few buttons on my clothes, because this hand cannot tie and untie the buttons; I can only wear clothes without buttons, my pants are all pull-ons, my wife and family have to help me, it is really difficult to untie the buttons. Every time when I wash vegetables, this hand hurts very uncomfortable. It’s so burdensome to do things.”(A7)

Patient felt guilty for his family and had a self-image disorder.

“Anyway I cannot do anything now, my wife is taking care of me, she is tired.” (A10)

“Is this hand still good control of all the skills? I can’t tell myself, because I felt the skin is getting darker and I felt that it was not so ugly before. You see this hand ah, with black and dry skin, sometimes it is embarrassing to show.” (A9)

Symptoms experience

Symptoms varied across patients and had different impacts on individual lives. The following are some common symptoms experienced by the included patients [39, 41].

Pain

“Is not able to sleep well, at, the foot hurt at night, really don’t know what to do for a long time, I could not sleep well, due to the pain at night, cold pain.” (A8)

Itching feeling peeling

“Sometimes it is itchy and can see dander on your hands. When you take off cloth, the dander is all over the place.” (A6)

Social and family aspects

This refers to the persistence of HFS symptoms, resulting in a lack of confidence in life among patients [42].

Limited social interaction

“I need help for numbness relief from the beginning, I do not look outside the windows now, my hands and feet cannot stand the cold weather, now I am not looking forward to going outside. I used to enjoy taking a walk, but now I don’t go, so I stay at home. “My performance is impacted. It directly affects work and income.“(A10)

Impacted family relationships

“They do not let me help with my little granddaughter. I feel I am useless.” (A1)

Experience dealing with symptoms

In the process of long-term symptom management, patients gradually found a balance between dealing with symptoms and maintaining a normal life to better adapt to life with illness [43].

Independently obtain disease knowledge

HFS patients acquire related knowledge via websites, physicians, and among patients [44, 45].

“I’ve been applying ointment, and recommended to the patient next to me, they said they did as well and I bought the same gloves as they used, it was quite helpful during the outbreak.” (A3)

“Always in control, but with no effect on flare. My daughter-in-law bought a skin lotions for me to apply.” (A8)

“I just checked it on my phone, saw what was on the Internet, and then tried it for myself, some were pretty useful.”(A15)

Change habits

“Now used to wear gloves, I do not touch cold, hot water at home to change into velvet gloves.” (A8)

Expectations for future

During the interview, the patients showed improved symptoms and met/exceeded the expectations of the healthcare providers.” [35].

“I always hope to have a way to make him better, at least let me sleep better at night, if you have any new way to tell me ah! Or do other patients have suggestions?” (A8)

“I just hope that there is a better solution to this problem. Otherwise, the constant dose reduction of chemotherapy drugs is not the way to go.”(A20)

“Help me think about reducing the cracking pain in my hands and feet. My life is really inconvenient. You’d better tell me something about this problem, I don’t know why at the beginning, or what to ask. Can you say something more, so we know something and feel more assured?” (A7)

“I was in the hospital before, but when I came home, I did not know who to ask (if I have any questions). I hope you can provide a channel to us patients, otherwise we do not know where and how to reach out for this problem.”(A13)

“In fact, I want to ask your nurse for some questions, but sometimes I do not know how to contact you, sometime, it is less embarrassing to call the nurse deck. It’s convenient to have contact information of a doctor.”(A15)

Education on symptom management can improve the self-management ability of patients who suffer from HFS [46-48]

In this study, by interviewing the 22 included patients, we observed the responses and attitudes of various patients. In these interviews, it was found that patients with HFS had insufficient knowledge and poor compliance [27]. Furthermore, some patients looked for information from peers who shared a similar experience and may rely on self-exploration. The accuracy of this information remains to be evaluated. Therefore, to achieve HFS symptom self-management, healthcare providers could actively provide professional advice and patient education through treatment, internet platforms, or collaboration with social welfare organizations. Such activities may increase patient awareness and improve disease management strategies [1, 2]. This study showed that symptom management education (SME), which provides patients with knowledge and skills on symptom management, could improve the self-management ability of patients, thereby reducing the burden and severity of symptoms. SME could also help delay the decline in the efficacy of patient self-management and improve their quality of life [43, 49]. A study on symptom self-management, self-efficacy, and symptom distress in cancer patients showed that higher self-efficacy is associated with lower symptom incidence, symptom distress, and higher overall health level and quality of life [49].

Improving patients’ the capability to identify early HFS symptoms and promote lifestyle changes

HFS is a chronic adverse reaction to chemotherapy. Some patients show acceptance and adaptation to the symptoms; however, others exhibit anxiety and worry. Previous studies [10] have shown that skin damage is a primary cause of patient discomfort. However, since skin damage may not be as disturbing as other symptoms such as nausea, vomiting, and pain, it might be easily ignored and thereby result in long-term complications [50]. The skin damage of HFS patients is not limited to changes on the skin surface, such as erythema, pigmentation, ulceration, and bleeding, but also involves sensory abnormalities such as tingling and numbness. The impact of these symptoms on patients is multifaceted, as it affects work-related activities, emotions, family relationships, and social entertainment. Moreover, when the body bears a certain discomfort, such as the symptoms of HFS [51], it may have an impact on the emotions of patients. A depressive emotional state could delay disease remission, thereby causing further impact on the body, and thus, initiating a vicious circle. A negative emotional state may cause excessive secretion of skin sweat glands in the hands and feet [28]. Currently, the mechanism of HFS is still unknown, but some studies suggest that it is possibly due to the increased penetration of chemotherapeutic drugs into the hands and feet where there are abundant sweat glands（1）. This accumulation might lead to adverse reactions to chemotherapy drugs on the hands and feet [52]. Therefore, in clinical settings, nursing staff should implement holistic care to maintain patients’ positive emotional states. This may also help patients to identify early HFS-related symptoms. Such interventions could be applied to specialty nursing according to the severity of the patient-specific symptoms [2].

Extensive social support is a favorable factor for improving the symptom management of patients with HFS

Patients have certain expectations of their healthcare providers regarding symptom improvement and emotional support. Doctors and nurses could communicate openly with patients about their condition and provide education. This finding is consistent with the report from Mücke et al. [4, 53], in which cancer patients with adverse reactions after medication needed information and emotional support. Patients expected that healthcare providers should provide good supportive communication, in addition to active listening and providing clear information about the treatment and possible adverse reactions. We found that these patients also expected healthcare providers to offer individualized care and establish good communication and relationships. These methods are essential to minimizing misunderstandings and promoting symptom improvement [8].

Meet the home needs of patients with HFS for symptom management through mobile healthcare

In the（Corona Virus Disease 2019，COVID-19）era[54], there is a special need for symptom management [27, 46]. The adverse reactions following chemotherapy differ. The management situation especially was exacerbated by the COVID-19 epidemic control, when it was challenging for patients to seek in-person treatment. Patients hoped that in addition to the treatment measures in the hospital, healthcare providers could also provide consultations, disease symptom monitoring, auxiliary patient treatment, psychological counseling, and other measures at home. Healthcare providers need to establish and improve information communication channels with the patients and their families to accurately assess the patient’s condition, and to conduct telemediation/consultation via video calls. Current internet technology provides new opportunities for the diagnosis, treatment, and management of chronic diseases. The use of information platforms for chronic disease prevention, control, and management has significantly matured. A previous study showed that telehealth interventions, which provide a communication platform between healthcare providers and patients at home, could effectively improve treatment compliance in HFS patients [27] and promotes independent disease management by patients. In addition, the interview results also confirmed that some patients with HFS were not able to identify certain symptoms in the early stage [55, 56]. In addition, it is recommended that healthcare providers actively and effectively communicate with patients and their families; understand the patients’ situations; conduct psychological counseling and encourage patients to actively face the condition and cooperate with the treatment; and inform patients about the methods for protection and pain relief, and ask their families to closely monitor the condition. It is also recommended that patients notify healthcare providers promptly when there are abnormal conditions [57, 58]. After the patient’s condition is improved or cured, routine follow-up is recommended to avoid and identify hidden diseases that may impact their health. This will also help patients to initiate treatment at an early stage and ensure that patients who stay home alone also receive active and effective disease management [4, 35].

HFS is not a terminal disease, but symptoms such as pain, ulcers, numbness impact the quality of life of patients. This also leads to a decline in self-care, increased depression, social disorders, and fear of chemotherapy. Therefore, prevention and management of HFS are crucial from the perspective of the patients’ day-to-day activities. This study described the HFS patient disease experience through qualitative research interviews. From these interviews, we concluded that healthcare providers should help patients to better treat the occurrence of HFS symptoms, actively participate in the management of HFS symptoms, and fully grasp the relevant information to HFS symptoms. In addition, healthcare providers need to provide HFS-related patient education and emotional support. Moreover, the development and popularization of information technology have provided new opportunities for symptom management. Healthcare providers should actively use the available internet platform to explore new models of disease management [59].

ACKNOWLEDGEMENTS

The authors thank all participating clinicians for their support. We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.

ETHICAL CONSIDERATION

The studies involving human participants were reviewed and approved by the Ethics Committee of Ruijin Hospital. The patients/participants provided their written formed consent to participate in this study. Written informed consent was obtained from the individual (s) for the publication of any potentially identifiable images or data included in this article.

DISCLOSURES

The authors declare that they have no competing interests.

AUTHOR CONTRIBUTIONS

Study design: Ji Zhang, C Wang, M Wang, L Huang，Ju Zhang. Data collection:Ji Zhang, C Wang, QY He, DL Mao;Data analysis: Ji Zhang. Study supervision: M Wang, L Huang. Manuscript writing: Ji Zhang. Critical revisions for important intellectual content: M Wang, L Huang.

DATA AVAILABILITY STATEMENT

The datasets presented in this article are not readily available because the original data for this study were used under license and are not publicly available. Requests to access the datasets should be directed to JiZ, [email protected].

Funding: This work was supported by the Nursing Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China (No. RJHK-2021-25).

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Table 1 Demographic and clinical characteristics (n=22)

Variables	N (%)
Age
Youth (18–44 years)	5 (22.73)
Middle-aged (45–59 years)	4 (18.18)
Older adult (60+ years)	13 (59.09)
Gender
Female	9 (40.91)
Male	13 (59.09)
Employment status
Full-time and part-time	4 (18.18)
Unemployed/retired	18 (81.82)
Primary cancer diagnosis
Colon cancer	9 (40.91)
Rectal cancer	7 (31.82)
Breast cancer	1 (4.55)
Stomach cancer	3 (13.64)
Duodenal cancer	1 (4.55)
Cervical cancer	1 (4.55)
Metastasis/recurrence
Yes	15 (68.18)
No	7 (31.82)

TABLE 2 Socio-demographic characteristics of the participants

No.	Age (years)	Sex	HFS grade	Primary diagnosis	Tumour type	Treatment lines received	Regimen
P1	61	M	2	Rectal cancer	Rectum	≥50	FOLFOX (oxaliplatin + calcium folinate + fluorouracil) + CET (cyclophosphamide + epirubicin + paclitaxel)
P2	40	F	1	Breast cancer	Breast	≥5	TCH (carboplatin + docetaxel, taxotere + Herceptin)
P3	75	F	2	Cervical cancer	Cervix	≥5	Gemcitabine + bevacizumab
P4	50	M	3	Stomach cancer	Stomach	≥50	Herceptin + PX (capecitabine + cisplatin)
P5	61	M	1	Rectal cancer	Rectum	≤5	Erbitux + FOLFOX (oxaliplatin + calcium folinate + fluorouracil), capecitabine
P6	35	M	1	Colon cancer	Right colon	≤5	FOLFOX (oxaliplatin + calcium folinate + fluorouracil) + CET (cyclophosphamide + epirubicin + paclitaxel) + vemurafenib
P7	60	M	2	Colon cancer	Sigmoid colon	≥10	Erbitux + FOLFOXRI (oxaliplatin/fluorouracil + irinotecan)
P8	63	M	1	Colon cancer	Colon	≥10	FOLFIRI (Irinotecan + Fluorouracil + Calcium folinate)
P9	55	F	1	Duodenal cancer	Duodenum	≥10	Bevacizumab + FOLFIRI (Irinotecan + Fluorouracil + Calcium folinate)
P10	65	M	1	Colon cancer	Ascending colon	≥30	CET (cyclophosphamide + epirubicin + paclitaxel) + FOLFIRI (irinotecan + fluorouracil + calcium folinate)
P11	56	M	1	Colon cancer	Colon	≥5	XELOX (capecitabine + oxaliplatin)
P12	72	M	1	Colon cancer	Sigmoid colon	≥10	Bevacizumab + FOLFIRI (irinotecan + fluorouracil + Calcium folinate)
P13	36	F	1	Rectal cancer	Rectum	≥10	Bevacizumab + FOLFIRI (irinotecan + fluorouracil + calcium folinate)
P14	67	M	1	Colon cancer	Sigmoid colon	≥30	Bevacizumab + XELIRI (capecitabine + irinotecan)
P15	73	M	1	Colon cancer	Sigmoid colon	≥10	Bevacizumab + XELOX (capecitabine + oxaliplatin)
P16	64	F	1	Rectal cancer	Rectum	≥5	Erbitux + FOLFOX (oxaliplatin + calcium folinate + fluorouracil)
P17	64	F	3	Rectal cancer	Rectum	≥10	5-FU+CET (cyclophosphamide + epirubicin + paclitaxel)
P18	75	M	1	Colon cancer	Colon	≤5	Erbitux + FOLFOX (oxaliplatin + calcium folinate + fluorouracil)
P19	62	F	1	Rectal cancer	Rectum	≥10	5-FU+CET (cyclophosphamide + epirubicin + paclitaxel)
P20	34	F	1	Rectal cancer	Rectum	≥10	Bevacizumab + oxaliplatin + raltitrexed
P21	36	F	2	Stomach cancer	Stomach	≤5	PD1 + XELOX (capecitabine + oxaliplatin)
P22	54	M	1	Stomach cancer	Stomach	≤5	SOX (oxaliplatin + tegafur)

Ca, cancer; F, female; M, male; HFS, Hand-foot syndrome.

TABLE 3 Main questions in the semistructured in-depth interview

ID	Question
1	Can you talk about your experience or feeling about this symptom?
2	Do you have any successful experience in dealing with symptoms?
3	Do you think this symptom will change your work, family, mood, and life?
4	Where do you like to get support and help?

No competing interests reported.

A qualitative study of the symptom management in patients with chemotherapy-induced hand-foot syndrome

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Abstract

Purpose

methods

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INTRODUCTION

METHODS

RESULTS

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Conclusions

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Additional Declarations

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