【原】化疗相关手足综合征及靶向治疗相关手足皮肤反应的癌症患者未能满足感知需求:一项定性研究

Unmet needs of cancer patients with chemotherapy-related hand-foot syndrome and targeted therapy-related hand-foot skin reaction: A qualitative study

化疗相关手足综合征及靶向治疗相关手足皮肤反应的癌症患者未能满足感知需求:一项定性研究

ABSTRACT

Purpose

The objective of this qualitative study was to understand the perceived needs of advanced-stage cancer patients with chemotherapy-related hand-foot syndrome (HFS) and/or targeted therapy-related hand-foot skin reaction (HFSR).

Method

Face-to-face interviews were conducted with 20 outpatients with advanced/recurrent cancer and chemotherapy-related HFS and/or targeted therapy-related HFSR using a semi-structured interview guide at Keio University Hospital, Tokyo, Japan. Thematic analysis was used to analyse the data.

Results

The unmet needs of cancer patients with chemotherapy-related HFS and/or targeted therapy-related HFSR was identified through four themes: a sense of helplessness with persistent symptoms, noticeable appearance as a barrier to social participation, decreased willingness to work and continue treatment, and need of individual coping strategies.

Conclusion

This study revealed unmet needs of cancer patients with chemotherapy-related HFS and/or targeted therapy-related HFSR that are not often voiced. Health care providers should provide full information in advance and find the best coping strategy for individual patients.

Keywords

Hand-foot syndrome  Hand-foot skin reaction  Chemotherapy  Targeted therapy  Cancer Unmet needs  Qualitative research

摘要

目的

本研究的目的是了解化疗相关手足综合征（HFS）和/或靶向治疗相关手足皮肤反应（HFSR）的晚期癌症患者的感知需求。

方法

使用日本东京庆应义塾大学医院的半结构化访谈指南，对20名门诊患者进行面对面访谈，这些患者患有晚期/复发性癌症和化疗相关的HFS和/或靶向治疗相关的HFSR。采用主题分析法对数据进行分析。

结果

化疗相关HFS和/或靶向治疗相关HFSR的癌症患者，未满足的感知需求通过四个主题确定：持续症状的无助感，明显的社会参与障碍，工作和继续治疗意愿下降，需要个体应对策略。

结论

这项研究揭示了不经常说话的化疗相关的HFS和/或靶向治疗相关的HFSR癌症患者，他们的需求得不到满足。卫生保健服务者应事先准备好完整的信息，并为个别患者找到最佳的应对策略。

关键词

手足综合征 手足皮肤反应 化疗 靶向治疗 癌症 未满足需要 定性研究

Introduction

Hand-foot syndrome (HFS) is associated with traditional cytotoxic chemotherapies, including cytarabine, anthracyclines, fluoropyrimidines, and taxanes (McLellan et al., 2015). HFS is distinct from hand-foot skin reaction (HFSR) which is reversible (Gomez and Lacouture, 2011) and associated with multikinase inhibitors (e.g. sorafenib, sunitinib, and regorafenib) and BRAF inhibitors (e.g. vemurafenib and dabrafenib) (McLellan et al., 2015). Although HFS/HFSR is usually not life threatening (Hoesly et al., 2011; Chanprapaph et al., 2016), it can lead to the cessation of therapy or a dose reduction and impaired quality of life and treatment outcomes (Huang et al., 2018; Rosen et al., 2013). Optimum prevention and treatment strategies for HFS/HFSR are needed to enhance quality of life and treatment efficacy (Huang et al., 2018; De Wit, 2014).

前言

手足综合征（HFS）与传统的细胞毒性化疗有关，包括阿糖胞苷，蒽环类药物，氟尿嘧啶和紫杉烷。HFS不同于可逆的手足皮肤反应（HFSR），它与多激酶抑制剂和BRAF抑制剂相关。虽然HFS / HFSR通常不会危及生命，但它会导致治疗终止或减少剂量，降低生活质量和治疗效果。需要研究针对HFS / HFSR的最佳预防和治疗策略，以提高生活质量和治疗效果.

Despite no standard prevention for HFS/HFSR, recommendations for prevention and management of HFS through the use of specific drugs are available based on expert opinions and literature reviews which also emphasize the importance of management based on the accurate grading of HFS/HFSR and patient education given by healthcare teams (Nikolaou et al., 2016; McLellan et al., 2015). Charalambous and Charalambous (2016) reported that skin toxicities distorted patients’ daily activities and negatively affected on their self-image, social engagement, and intimate relationships. Another qualitative study also suggested that skin toxicities were related to actual physical discomfort, appearance concern, social isolation, and high medical morbidity (Coleman et al., 2011).

尽管没有HFS / HFSR的标准预防措施，但可以根据专家意见和文献综述，使用具体的预防和管理建议来提供药物，他们也强调基于HFS/HFSR的准确评分和医疗团队提供的患者教育的管理重要性。Charalambous 和Charalambous的研究表明，皮肤毒性破坏了患者的日常活动，对他们的自我形象，社交活动和亲密关系产生了负面影响。另一项定性研究还表明，皮肤毒性与身体不适，外观问题，孤僻和高发病率有关。

The literature suggests that HFS occurrence is a predictor of prolonged survival in patients with locally recurrent/metastatic breast cancer (Zielinski et al., 2016). According to the recent risk/benefit trade-off analyses, patients prefer a more efficacious therapy with more severe skin toxicities to a less efficacious therapy with less severe skin toxicities (Tischer et al., 2018). To our knowledge, there is no study on patients’ perspectives of skin toxicities focusing on HFS/HFSR during cancer therapy. Accordingly, we conducted a qualitative study to understand perceived needs of advanced-stage cancer patients with chemotherapy-related HFS and/or targeted therapy-related HFSR.

文献表明，HFS的发生是局部复发/转移性乳腺癌患者延长生存期的预测指标。根据最近的风险/利益权衡分析，患者更喜欢皮肤毒性更严重更有效的治疗，而不是毒性没那么严重效果相对较差的治疗。据我们所知，还没有针对HFS / HFSR癌症患者对皮肤毒性的看法进行研究。因此，我们进行了此项定性研究，以了解HFS和/或HFSR的晚期癌症患者的感知需求。

Methods

2.1. Study design

We conducted a qualitative study using individual interviews with outpatients with advanced/recurrent cancer and chemotherapy-related HFS and/or targeted therapy-related HFSR at Keio University Hospital, Tokyo, Japan. This study was approved by the Institutional Review Board of the Faculty of Nursing and Medical Care, Keio University (No. 267), and the Institutional Review Board of the Keio University School of Medicine (No. 20170251).

2方法

2.1试验设计

我们在日本东京的庆应义塾大学医院进行了这项定性研究，对晚期/复发性癌症和化疗相关HFS和/或靶向治疗相关HFSR的门诊患者进行了独立访谈。该研究得到了庆应义塾大学护理与医疗学院（第267号）的机构审查委员会和庆应义塾大学医学院的机构审查委员会（No. 20170251）的批准。

2.2. Setting and participants

Eligible participants were outpatients with chemotherapy-related HFS and/or targeted therapy-related HFSR aged 20 and older who did not have hearing or cognitive disorders and were able to agree or withdraw in regard to study participation. Patients who had strong physical pain, discomfort, anxiety, or depression were excluded. Potential participants were invited to meet the investigators of the study by their attending physicians at their visit to the Cancer Centre, Department of Gastroenterology and Hepatology, or Department of Dermatology, Keio University Hospital, Tokyo. One of the investigators (KY) explained the objective and methods (e.g. interview method and audiotaping) of the study to those who were interested in the study. Before obtaining the informed consent, four patients withdrew mainly because of ‘no time’. All approached participants gave their oral and written informed consent to participate in the study and chose a suitable date for the interview.

2.2设置和参与者

符合条件的参与者为20岁及以上的门诊患者，这些患者均为化疗相关手足综合征（HFS）和/或靶向治疗相关手足皮肤反应（HFSR）患者。他们没有听力或认知障碍，并且能够同意或退出参与研究。排除标准：身体有强烈疼痛，不适，焦虑或抑郁的患者。在访问东京庆应义塾大学医院癌症中心、消化内科和肝病科或皮肤科时，潜在的参与者被邀请与研究人员见面。其中一名调查人员（KY）向对研究感兴趣的人，解释该研究的目的和方法（例如访谈和录音）。在获得知情同意书之前，有4名患者因为“没时间”而退出。所有接触的参与者都给予口头和书面知情同意书，参与了研究并选择了合适的访谈日期。

2.3. Data collection

The investigators (HK and KY), with extensive experience in cancer field and qualitative study, conducted in-depth interviews with 20 patients using a semi-structured interview guide in a private room at the hospital between March and June 2018. After the completion of the 3rd, 8th, and 14th interviews, the investigators (HK and KY) conducted an interim analysis, and based on the results, we reviewed the interview guide and refined it to facilitate extracting unmet needs. The following questions were included in the interview guide: · What problems do you have with HFS/HFSR? · How does HFS/HFSR affect your daily life? What problems do you want to improve in your daily life? · Does the treatment, care or support for HFS/HFSR given by healthcare professionals meet your expectations? What do you want healthcare professionals to do for you? Emerging themes were discussed, and data collection continued until the data reached saturation (Moser and Korstjens, 2018). The interviews were audiotaped and transcribed verbatim.

2.3数据收集

研究人员（香港和肯塔基州）在癌症研究经验和定性研究方面拥有丰富经验，于2018年3月至6月期间，在医院的私人房间使用半结构化的访谈指南，对20名患者进行了深入访谈。在第3次，第8次和第14次访谈完成后，调查人员（香港和肯塔基州）进行了中期分析，并根据调查结果，我们查阅了访谈指南并对其进行了细化改进，以便于提取未满足的需求。访谈指南中包含以下问题：

你对HFS / HFSR有什么问题；HFS / HFSR如何影响您的日常生活；你想在日常生活中改善什么问题；医护人员对你HFS / HFSR的护理或支持是否符合您的期望？您希望医疗专业人员为您做什么？

研究也讨论了新的主题，数据收集一直持续到数据达到饱和（Moser和Korstjens，2018年）。采访被录音并逐字抄录。

2.4. Data analysis

To reveal the content of and meanings behind themes present across entire data sets, thematic analysis was used to analyse the data. After all the interview data were transcribed, the investigator (KY) anonymised personally identifiable information. We used the qualitative analysis software NVivo10® to organize codes and passages

2.4数据分析

为了发现整个数据呈现的主题内容和意义，使用主题分析法来分析数据。在所有访谈数据被转录后，调查者（KY）匿名了个人身份信息。我们使用定性分析软件NVivo10® 来组织准则和访谈短文。

To ensure the trustworthiness of the study, we adopted the following procedures: First, we reflected on preconception and preferences of the investigators about cancer patients and HFS/HFSR to minimize the bias, and made efforts to bracket the perceptions and subjectivity during analysing and interpreting the data. According to the principles of thematic analysis (Braun and Clarke, 2006), one of the investigators (KY) independently generated an initial list of codes and subthemes. Then, together with another investigator (HK) they reviewed and refined all codes, subthemes, and their corresponding passages for discrepancies in interpretation, until consensus was reached. The investigators combined related codes into larger thematic categories and confirmed that the data reached saturation. The themes were finalised by the peer debriefing of research team which included oncologists and dermatologists. The final themes and quotations that supported the themes were translated into English by a professional translator.

为了确保研究的可信度，我们采用了以下措施：首先，我们对先入为主进行了反思，以及调查人员对癌症患者和HFS / HFSR的偏好，以尽量减少偏见，并在分析和解释数据时将感知和主观性包括在内。根据主题分析的原则，其中一名调查者（KY）独立生成了准则和子主题的初始列表。然后，他们与另一名调查员（香港）一起审查并完善了所有准则，子主题及其在解释上的差异对应的短文，直至达成共识。调查人员将相关准则合并为更大的主题类别，并确认数据达到饱和。研究小组成员包括肿瘤学家和皮肤科医生，他们对研究主题进行了总结。最终确定的的主题和次主题的条目由专业翻译人员翻译成英语。

3 Results 

3.1. Participant characteristics 

Twenty participants (13 female and seven male) participated in this study. The mean age of the participants was 65.3 years (range: 36–83). The majority of the participants were employed (50%) and married (80%). Female participants accounted for 65%. The most common type of cancer was colon cancer (65%) followed by gastric cancer (20%). Participant demographic and clinical characteristics are described in Table 1 and Table 2, respectively. As shown in Table 2, 14 of 20 participants received both chemotherapy and targeted therapy, and most participants used multiple skin care products for HFS/HFSR grade 1 or 2. Mean interview duration was 26.6 min. Thematic analysis revealed four major themes (Fig. 1).

3结果

3.1参与者特征 

20名参与者（13名女性和7名男性）参加了这项研究。参与者的平均年龄为65.3岁（范围：36-83）。大多数参与者都有工作（50％）和已婚（80％）。女性参与者占65％。最常见的癌症类型是结肠癌（65％），其次是胃癌（20％）。参与者的人口统计学和临床特征描述分别见表格1和表2。如表2所示，20名参与者中的14名同时接受了化疗和靶向治疗，大多数参与者使用多种护肤产品用于HFS / HFSR 1级或2级，平均访谈持续时间为26.6分钟。主题分析显示了四个主要主题（图1).

3.2. A sense of helplessness with persistent symptoms

As hands and feet are used in everyday life, participants experienced pain and change in sensitivity that prevented them from doing some daily activities. One of the participants said, ‘Anticancer medications caused more distress than surgery. (Because of numbness and pain) I hardly walked.’ (P11, 70-year-old male). One of the participants said, ‘It is painful. I barely walk ….’ (P10, 67-year-old female). Another participant described the inconvenience: ‘It is frustrating and stressful. Hand movements affect everything. For example, opening a bag or a zip, taking something out, or turning something.’ (P5, 68-year-old female).This participant felt that she was just the same as her 90-year-old mother who had difficulty in taking out her medications

3.2 一种持续症状的无助感

由于日常生活中会常用到手和脚，参与者经历了疼痛和敏感的变化，这妨碍了他们做一些日常活动。其中一位参与者说，抗癌药物比手术带来了更多的痛苦。（因为麻木和疼痛）我几乎走不动。（P11,70岁男性）还有一位参与者说，“我勉强能走路，这十分痛苦......（P10,67岁女性）另一位参与者描述了造成的不便：“真的让人很沮丧、很有压力，因为手部动作会影响一切。例如，打开一个包或拉链，取出东西，或转动一些东西。（P5,68岁的女性），这位参与者认为她和她90岁的母亲一样，在服用药物方面有困难。

Participants were at a complete loss as what to do with persistent HFS/HFSR. Without frequent skin care, HFS is easily worsened. Participants were frustrated that treatment does not cure HFS, and felt helpless. One of the participants had received the current chemotherapy and targeted therapy regime for four years. She used hand cream and band aids for cracked and dry skin on her hands and feet, but the condition was not improved. She was determined to ask her attending physician and be referred to a dermatologist. Although she understood that her condition might not improve during her cancer therapy, the frequent use of hands made her daily living difficult. She said, ‘I don't know what to do about the persistent terrible condition. It is not getting better at all. Hirudoid doesn't work at all. But I can't wear gloves all the time. I don't know what to do.’ (P1, 48-year-old female).

 参与者完全不知道如何处理持续性HFS/HFSR。如果不经常对皮肤护理，HFS很容易恶化。参与者对无法治愈HFS感到沮丧，并十分无助。其中一名参与者已接受目前的化疗和靶向治疗方案四年。她用护手霜和创可贴治疗手脚干裂的皮肤，但病情却没有改善。她决心要求主治医生将其转诊给皮肤科医生。虽然她明白自己的病情在癌症治疗期间可能没有改善，但经常使用干裂双手使她的日常生活变得困难。她说，“我不知道如何是好，情况一点也没有好转，喜疗妥根本不起作用。但我不能一直戴手套，我不知道下一步该怎么办。”（P1,48岁的女性）。

Another participant also used gloves but found difficulty. She said ‘When it is rubbed by the gloves like this, the nails on my fingers are painful. The skin care product seems to work for only one or two days. I experience this repeated cycle.’ (P5, 68-year-old female). All participants felt a sense of helplessness. ‘Skin problems are beyond my control. It works against my efforts … ’ (P17, 62-year-old male).

另一名参与者也使用了手套，但发现有困难。她说，“当用这样的手套擦拭时，我的指甲就很痛。这种护肤品只能使用一两天，我经历过这种重复的循环。（P5,68岁的女性）。所有参与者都感到无助，“我无法解决皮肤问题”。（P17,62岁的男性）。

Participants suffered from a feeling of discomfort from the sticky skin care products. Frequent application was necessary, but it adhered to everything. One of the participants described it as follows: ‘I can't do anything with my bare hands because the drug (skin care product) is sticky. So, I wear white cotton gloves all the time. Otherwise, the drug sticks to everything, and it's sticky.’ (P5, 68-year-old female). She used skin care products every morning, afternoon, and evening, so she had to wear gloves all day and night. A working participant had to reduce the number of applications because it affected her work: ‘I often use a PC for my work so I can't use the drug (skin care product) much or sometimes do not use it because it is sticky.’ (P9, 36-year-old female).

参与者因使用这些粘稠的护肤品而感到不舒服。经常使用这种护肤品是必要的，但是它会粘附任何手里要拿的东西。其中一位参与者描述到：'由于药物（护肤品）粘稠，我无法用双手做任何事。所以，我一直都戴着白色棉手套。否则，药物会粘在任何东西上，而且很粘。（P5,68岁的女性）。她每天早上，下午和晚上都使用护肤品，因此她必须整天戴着手套。一个有工作的参与者不得不减少使用药物的数量，因为这影响到她的工作：“我经常使用PC工作，所以我不能使用太多药物（护肤品），或者有时不使用它，因为它们太粘了。”（P9,36岁女性）。

Despite much discomfort and inconvenience in daily living, participants did not feel that the drug was effective, as one of the participants (ointment, lotion, and cream were prescribed) said, ‘I think that they (skin reactions) do not disappear with the prescribed drugs.’ (P5, 68-year-old female). Another participant revealed that the hardest thing was that there were no effective drugs for skin reactions: which was the same situation with cancer: ‘My hands are getting darker and darker, swollen and painful. But there are no effective drugs.’ (P7, 61- year-old female). Participants desperately wanted a drug to cure these skin symptoms: ‘Development of a new drug that can cure the skin problems is the only way.’ (P17, 62-year-old male).

尽管使用药物在日常生活中有很多不适和不便，但是参与者并不觉得这种药物是有效的。正如一名参与者（软膏，乳液和乳膏处方）所说，“我认为它们（皮肤反应）不会随着处方药的使用而消失。”（P5,68岁的女性）。另一位参与者透露，最难的是没有有效的药物治疗皮肤反应，这与癌症的情况相同：'我的手越来越黑，还肿胀和疼痛，但是没有有效的药物能够治疗。（P7,61岁的女性）。参与者迫切需要一种药物来治疗这些皮肤症状：研发一种可以治愈皮肤问题的新药是唯一的解决方法。（P17,62岁男性）

Since the exacerbation of HFS/HFSR may lead to dose reduction or drug change in cancer therapy, participants spend time managing HFS/ HFSR. They felt stressed about always having to pay attention to their skin condition and providing frequent self-care to avoid it worsening. ‘If I forget to use the drug (skin care product), my hands get cracked. Once the skin is cracked, it is difficult to repair it. So, I try not to do so.’ (P12, 71-year-old male). The burden of self-care occupied their everyday life: ‘To avoid it (bleeding), I had to put on the cream so often. I had to have it in my mind all the time. It was so stressful.’ (P1, 48-year-old female).

由于HFS / HFSR的恶化可能导致癌症治疗中的服药减少或换药，因此参与者需要花时间管理HFS / HFSR。他们必须时刻关注自己的皮肤状况，并经常进行自我护理以避免皮肤病情恶化，因此常感到很有压力。如果我忘了使用这种药（护肤品），我的手就会破裂。一旦皮肤破裂，就很难恢复。所以，我尽量时刻关注自我护理。（P12,71岁男性）自我护理的负担占据了他们的日常生活：为了避免它（流血），我不得不经常使用护手霜，还不得不一直想着这件事，这样太有压力了。（P1,48岁的女性）。

3.3  Noticeable appearance as a barrier to social participation

 Since hands are visible parts of the body, participants were concerned that other people stared at their altered hands. ‘When the condition is bad, I use four band aids for each hand. That means eight band aids for my hands. I can't use my fingers as usual. It is not convenient … People think, “Poor woman with eight band aids.”’ (P1, 48-year-old female). One of the participants said, ‘When it is darker, I don't like that people may be thinking, “It's dark” … I am concerned that people think something is wrong with me.’ (P13, 61-year-old female). Participants did not want other people to pry into their skin symptoms. They were sometimes misjudged as being a dirty person. ‘If I tell people about the disease, they understand that the darkness due to the disease and it's OK. But people who do not know the reason are likely to think that it is because of poor hygiene. “Oh, this man has dirty hands.” So I wear gloves to hide my hands.’ (P11, 70-year-old male).

3.3明显的社会参与障碍

由于手是身体的可见部位，参与者担心其他人盯着他们患病的手看。当情况不好时，我每只手使用四个邦迪创可贴。这意味着我的双手要用8个邦迪创可贴。我不能像往常那样使用我的手，因为太不方便......人们会认为，“带着八个创可贴的可怜的女人。”（P1,48岁的女性）。其中一位参与者说，“当手变黑时，我不喜欢别人会想到，她手是黑的......“我担心人们会认为我有问题。”（P13,61岁女性）参与者不希望其他人窥探他们的皮肤症状，他们有时被误认为是一个肮脏的人。“如果我告诉人们这种疾病，他们就会明白是由于疾病导致的手部变黑，这这没什么大不了的。但是，不知道的人可能认为这是因为不讲卫生。“哦，这个男人手很脏，所以我戴着手套。（P11,70岁男性）。

Embarrassment led to hiding the affected hands and there were negative effects on their social life. One of the participants said, ‘It is depressing because it is clearly dark. My (finger) joints get dark. It's even worse. So, I paint my nails to cover it when I see somebody.’ (P7, 61-year-old female). However, she found ‘no means to hide it because they are hands.’ Participants were also tired of being asked about their condition and having to give an answer every time. ‘If the condition was not so bad and not so visible, people wouldn't notice it. But it is visible, so people ask me, “What's the matter with you?” and I reply. Such repetition is stressful.’ (P1, 48-year-old female).

因为避免尴尬隐藏受疾病影响的手，对患者的社交生活产生了负面影响。其中一位参与者说，“这令人十分沮丧，因为手显然是黑色的。情况更糟的是我的（手指）关节变黑了。所以，当我要见人的时候，会涂指甲来掩盖它。（P7,61岁的女性）。然而，她发现“根本没有办法隐藏它，因为它们是手。”参与者也厌倦了被问及他们的状况并且每次都必须给出答案。“如果情况不是那么糟糕而且不那么明显，人们就不会注意到它。但它是显而易见的，所以人们问我，“你怎么了？”然后我一一回答。这种重复回复让我压力很大。（P1,48岁的女性）。

3.4  Decreased willingness to work and continue treatment

 HFS affected participants' work. In particular, pain and perceptive change not only reduced working capacity but also their willingness to work: ‘Pain discourages my willingness. I lose my drive for everything including work.’(P14, 65-year-old male). A mechanic was worried that he might be a burden rather than contributing to productivity. He said, ‘I have to use my hands for work … Yes, it is critical … I am losing the ability to feel what I touch. It is hard. It hinders my work. I have to decrease such kind of work. I barely go to work.’ (P8, 46-year-old male). Another participant tried to think his condition was not bad and encouraged himself to continue treatment. However, he said, ‘If it continues forever, it is annoying. Typing errors are increasing. I have to write an article with 800 characters today, but it is bothersome and I may not do it.’ (P4, 59-year-old male).

3.4 工作和继续治疗意愿下降

HFS影响了参与者的工作。特别是疼痛和感知变化不仅降低了工作能力，而且降低了他们的工作意愿。“痛苦阻碍了我的心愿，我失去了对待包括工作在内的一切动力。'（P14,65岁男性）。一名机修工担心他可能会成为负担，而不能提高生产率。他说，'我必须用我的双手工作......是的，这很关键......我正在失去触摸东西的能力。它妨碍了我的工作，我不得不减少这种工作，所以，我几乎不再去上班。（P8,46岁男性）另一名参与者试图认为自己的病情状况不错，并鼓励自己继续接受治疗。然而，他说，“如果这种情况永远持续下去，那就太烦人了，打字错误越来越多，今天我必须写一篇800字的文章，但这很麻烦，我可能做不到。（P4,59岁男性）

Because of a great impact of HFS/HFSR on daily activities, some participants reviewed the meaning of anticancer therapies: ‘Persistent side effects are depressing because I can't do anything. I wonder whether treatment is meaningful because my condition is so bad.’ (P13, 61- year-old female).

由于HFS / HFSR对日常活动的影响巨大，一些参与者回顾了对抗癌治疗的认识：“持续的副作用令人沮丧，因为我对此无能为力。我不知道治疗是否有意义，因为我的病情现在非常糟糕。”（P13,61岁女性）

3.5. Need for individual coping strategies

Participants want specific information on the outlook of HFS/HFSR. They want to know how the symptoms of HFS/HFSR will change, worsen or improve during the period of cancer treatment. They did not have enough information to decide dose reduction or discontinuation of anticancer therapy. One of the participants said, ‘This is the 10th course (of chemotherapy and targeted therapy). It is getting worse. I am worried how far it will go. If I am informed and given guidance, it would offer me some relief.’ (P7, 61-year-old female). Another participant read the leaflet given by the healthcare provider but could not judge whether she should stop medication. ‘The doctor prescribes many kinds of medicines … The leaflet said that I should stop “if a prickly condition develops”. I wonder my condition is applicable. I need a more detailed explanation from the healthcare provider. I can't judge by myself.‘(P15, 71-year-old female).

3.5需要个体应对策略

参加者希望获得有关HFS / HFSR前景的详细资料。他们想知道在癌症治疗期间HFS / HFSR的症状将如何变化、恶化或改善。他们没有足够的依据来决定减少服药剂量或停止抗癌治疗。其中一位参与者说，“这是第10个疗程（化疗和靶向治疗），情况越来越糟，我担心还能走多远。如果我能获得护理资料并给予指导，我会得到一些解脱。（P7,61岁的女性）。另一位参与者阅读了医护人员提供的说明书，但无法判断她是否应该停药。“医生开了很多种药......说明书中说我如果出现刺痛症状应该停止用药。但我不知道我的情况是否适用，自己根本不能判断，我需要医护人员提供更详细的说明。（P15,71岁的女性）。

Participants were seeking coping strategies and trying to find their own coping strategies by themselves. One of the participants said, ‘Maybe I know better than the nurse. When I say that I am doing this, the nurse says “Oh, that's a good idea.” I know that the nurse is busy, so she does not tell me what to do from one to 10.’ (P19, 68-year-old female). She wished that the healthcare provider would give her a list of management methods.

参与者正在寻求应对策略，并试图找到适合自己的应对策略。其中一位参与者说，'也许我比护士更了解我自己的情况。当我说我这样做时，护士说，“哦，这是个好主意。”我知道护士很忙，所以她不告诉我从一个到十做什么。（P19,68岁的女性）。她希望医护人员能给她一份管理方法清单。

4.Discussion

This study reveals that patients cry for help with persistent skin symptoms. HFS/HFSR restricts cancer patients’ daily activities, impairs their social functioning (Sibaud et al., 2011; Nardone et al., 2012), and has psychosocial consequences that can lead to a reduced quality of life (Sehgal et al., 2009). As hands are an integral part of our personal and social life (Ahmed et al., 2015) and feet are related to mobility, the present study found that HFS/HFSR negatively affected almost every activity of daily life. Moreover, the participants were stressed about visible hand symptoms that might be misinterpreted by other people. Telling others that the skin symptoms were caused by cancer treatment was also a psychological burden for the participants.

4讨论

这项研究表明，患者在持续的皮肤症状中会哭喊求助。HFS / HFSR会限制癌症患者的日常活动，损害其社会功能，并可导致生活质量下降的心理社会后果。由于手是我们个人和社交生活中不可或缺的一部分，而脚与移动有关，本研究发现HFS / HFSR几乎对日常生活中的每一项活动都有负面影响。此外，参与者对可能被其他人误解的可见手部症状感到有压力。告诉其他人皮肤症状是由癌症治疗引起的，对参与者来来说也是一种心理负担。

Interestingly, this study suggests that HFS/HFSR is related to a loss of productivity and questions the meaning of cancer treatment. Persistent painful symptoms reduce the willingness of patients to continue treatment and work. Some participants began to question whether the current cancer treatment was really needed if the trade-off was persistent with terrible skin symptoms, because the treatment goal was often to improve survival and to maintain or improve quality of life for patients with advanced cancer.

不可思议的是，这项研究表明HFS / HFSR与生产力的丧失及质疑癌症治疗意义有关。持续的疼痛症状会降低患者继续治疗和工作的意愿。一些参与者开始质疑，如果皮肤症状很糟糕的情况下，且这种状况持续存在的话，那么目前的癌症治疗是否真的必要，因为治疗目标通常是提高生存率、维持或改善晚期癌症患者的生活质量。

Patients are suffering not only from skin symptoms but also from caring for the skin with the skin care products. The high level of burden caused by skin care could lead to reduction of the number of drug applications or discontinuation. However, such decision-making is difficult for patients with advanced cancer. In clinical settings, specific information is often not provided to patients to help with their decisionmaking. Although patients understand their symptoms, they are not sure whether they have the specific symptoms that the physician and nurse have told them to pay attention to. In the present study, some participants hesitated to talk about their skin symptoms with their physician. Even though they received skin treatment, the skin care product was not as effective as they expected and they often sought their own coping strategies by themselves. The participants in this study recognized the importance of moisturizers by themselves and frequently used them. Indeed, skin care with moisturizers improves skin barrier function and hydration (Bensadoun et al., 2013).

患者不仅受到皮肤症状的困扰，而且还要受到使用护肤品护理皮肤的困扰。皮肤护理造成的高负担可能导致药物应用数量减少或停药。然而，对于晚期癌症患者来说这种决策是困难的。在临床环境中，通常不向患者提供具体信息以帮助他们做出决策。虽然患者了解自己的症状，但他们不确定他们是否具有医生和护士告诉他们要注意的特定症状。在本研究中，一些参与者不愿与他们的医生谈论他们的皮肤症状。尽管他们接受了皮肤治疗，但效果并不像他们预期的那样有效，他们经常自己寻求适合自己的应对策略。本研究的参与者自己认识到润肤霜的重要性，并经常使用它们。事实上，润肤霜可以改善皮肤屏障功能而具有保湿效果.

The difference of attitudes and perceptions about skin toxicities between the patient and the healthcare provider is often reported (Basch et al., 2009; DiMaio et al., 2015; Tischer et al., 2018). As standard practice, patients are informed about skin protection and observation of HFS/HFSR; however, they do not know what to do with persistent HFS/HFSR. While specific indicators are required for selfidentification of skin symptoms, effective health education should be offered to patients for appropriate use of the drug to minimize discomfort in daily skin care. Since optimal management remains uncertain aside from dose reduction and treatment interruption, healthcare providers should seek suitable coping strategies for individual patients. In this study, most participants had Grade 1 skin toxicities. Only one third of them were referred to the dermatologist, and the rest was treated by the oncologist. Skin care education for the oncology team based on appropriate drug selection and use, including order, volume, and interval in skin care is necessary. In addition, future clinical trials are needed to address appropriate interventions for the management of HFS/HFSR (Hofheinz et al., 2015; Chanprapaph et al., 2016). Furthermore, development of a cream that minimizes discomfort and impacts on daily living is desirable.

经常会有报道患者和医护人员之间对皮肤毒性的态度和看法的差异。作为标准做法，患者需要被告知皮肤保护和HFS / HFSR的观察;但是，他们不知道如何处理持久性的HFS / HFSR。虽然皮肤症状的自我识别需要特定的指标，但应为患者提供有效的健康教育，以便适当使用药物，减少不当的日常皮肤护理行为。由于除了剂量减少和停止治疗之外，仍然不确定最佳管理方法，医护人员应该为每个患者寻求合适的应对策略。在这项研究中，大多数参与者都有一级皮肤毒性，其中只有三分之一的病人被转诊给皮肤科医生，其余的则由肿瘤科医生治疗。在适当的药物选择和使用，包括皮肤护理的顺序、体积和间隔方面，对肿瘤科团队进行皮肤护理教育是必要的。此外，需要进一步的临床试验来解决HFS / HFSR管理的适当干预措施。而且，期望开发一种能将不适感和对日常生活的影响最小的乳膏。

This study has several limitations. As with all qualitative studies, our sample size was small. In addition, the selection of the participant population and of a single institution might influence the results of the study. Since all the participants had metastasis and recurrence and talked about symptoms other than skin toxicities, it was very difficult to isolate the experience of HFS/HFSR. Most of the participants received both chemotherapy and targeted therapy and did not take biopsies, we did not know clearly whether they developed a HFS or HFSR or both. In addition, whether the hands, feet or both were affected was not specifically described in the medical chart. The participants used multiple skin care products and we could not identify which one caused discomfort (e.g. stickiness).

这项研究有几个局限性。与所有定性研究一样，我们的样本量很小。此外，参与者选择和单一机构的选择可能会影响研究结果。由于所有参与者都有转移和复发，并且谈论的是皮肤毒性以外的症状，因此很难分离出HFS / HFSR的经验。大多数参与者同时接受了化疗和靶向治疗，并且未进行活检，我们不清楚他们是否发展为HFS或HFSR或两者兼而有之。此外，医学图表中对手，脚或两者是否受到影响没有具体描述。参与者使用了多种护肤产品，我们无法确定哪一种引起了了不适（如粘性）。

5 Conclusions 

This study revealed unmet needs of cancer patients with chemotherapy-related HFS and/or targeted therapy-related HFSR that were not often voiced. Persistent and visible symptoms of HFS/HFSR seriously hinder patients' daily activities including work and social functions. The physical and psychological burden of HFS/HFSR even leads to patients questioning the meaning of cancer treatment. To meet the unmet needs of patients, first, full information should be given at the beginning of the cancer therapy so that the patients are prepared for management of HFS/HFSR. Second, indicators help patients for selfidentification of HFS/HFSR. Third, healthcare providers should carefully listen to patients’ problems and find the best coping strategy for each individual patient.

5结论

这项研究揭示了化疗相关的HFS和/或靶向治疗相关HFSR的癌症患者未满足的需求，这些患者并不经常表达。HFS / HFSR的持续和可见症状，严重影响患者的工作和社会功能等日常活动。HFS / HFSR的身体和心理负担甚至导致患者质疑癌症治疗的意义。为了满足患者未被满足的需求，首先，应在癌症治疗开始时提供全面的信息，以便患者为HFS / HFSR的治疗做好准备。其次，指标有助于患者自我识别HFS / HFSR。第三，医疗保健提供者应该仔细倾听患者的问题，并为每个患者找到最佳的应对策略。