Experiences of immune-related skin toxicity: a qualitative study among patients with cancer

Experiences of immune-related skin toxicity: a qualitative study among patients with cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Experiences of immune-related skin toxicity: a qualitative study among patients with cancer Zhihui Yang, Ruiqi Lu, Xingwen Li, Suting Liu, Yuanyuan Luo, Ziqi Wang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3899394/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Immunotherapy has changed the outlook for cancer treatment. A closer look at the accompanying symptoms from the patient’s perspective is necessary to improve their tolerance to treatment and is the basis for standardized symptom management. Objective To describe the symptomatic experience of skin toxicity in cancer patients undergoing immunotherapy. Design: Qualitative interviews on symptom experiences were conducted from the perspective of cancer patients receiving immunotherapy. Methods A purposive sample of 18 patients with immune-related cutaneous adverse events participated in this semi-structured interview. Transcripts were entered into NVivo 11.0. Qualitative thematic analysis was used to analyze the data for significant statements and phrases, which were organized into themes and subthemes. Results Three main themes were identified in the data: (I) management of skin toxicity in patients; (II) patients’ experience of skin toxicity; and (III) problems that skin toxicity poses for patients and the support they would like to receive. Conclusions The result enables nurses to better understand and empathize with the patient’s experience, to truly practice the essence of patient-centered care, and provide a basis for the development of standardized symptom management programs in the future. Neoplasms Immunotherapy Skin Qualitative research Background According to Global Cancer Statistics, there has been a rapid increase in the incidence and mortality rate of cancer worldwide [ 1 ]. In 2022, approximately 4.82 million new cancer cases were recorded in China [ 2 ]. Among numerous immunotherapeutic strategies, immune checkpoint blockade has shown remarkable benefits in the treatment of different types of cancer. In recent years, immune checkpoint inhibitors have emerged as a promising antitumor therapy following surgery, radiotherapy, chemotherapy, and targeted therapy [ 3 ]. These inhibitors have revolutionized cancer treatment, providing a positive response for 25% of patients. Currently, immune checkpoint inhibitors are approved by the US Food and Drug Administration for treatment of eight types of cancer [ 4 ]. Immune checkpoint inhibitors have distinct mechanisms of action compared to standard anticancer therapies. By increasing the activity of the immune system, immune checkpoint blockade can induce inflammatory side-effects termed immune-related adverse events. The gastrointestinal tract, endocrine glands, skin, and liver are the organ systems most affected by these adverse events [ 5 ]. Aside from their impact on patients’ quality of life, severe cases of immune-related adverse events can lead to a reduction or discontinuation of antitumor medications, affecting the progress of treatment [ 6 – 8 ]. Immune-related cutaneous adverse events are an early form of immune-related adverse events, which include pruritus, rash, and reactivity skin capillary endotheliosis, oral mucosal lichenoid reaction and Sjögren’s syndrome, bullous pemphigoid, vitiligo, and Stevens–Johnson syndrome [ 8 , 9 ]. In one study, the incidence of immune-related cutaneous adverse events was 43–45% in patients treated with CTLA-4 inhibitors and approximately 18–23% in patients treated with PD-1 inhibitors [ 10 ]. The median time to onset varies among the various types of skin toxicity, with most symptoms appearing early during treatment [ 11 ]. Skin toxicity occurs on average 3–4 weeks after the start of treatment [ 12 ]. Most cutaneous toxicity reactions are classified as grades 1–2, whereas adverse events of grades 3–4 are rarely reported. Severe cutaneous adverse events are less common but are important to recognize and treat promptly [ 13 ]. Patients experiencing skin toxicity can become annoyed and frustrated; severe skin toxicity can cause patients to worry about the long-term effects of immunotherapy, and skin discomfort may limit their activities [ 14 ]. Furthermore, patients often must return to the hospital for examination or treatment due to adverse skin events, increasing the cost and burden of their treatment [ 13 , 15 ]. The current research mainly focuses on exploring the incidence and influencing factors of adverse reactions, and there are also some qualitative studies on patient experiences. However, there are limited qualitative studies focusing on the patient experience of immune-related skin toxicity. Since skin toxicity is the most common adverse event, gaining a deeper understanding of patients' perspectives is of great significance for subsequent symptom management. Methods Design and setting A qualitative descriptive design was utilized in this study, which took place at a comprehensive cancer treatment facility in Southern China. The hospital is renowned for its expertise in providing medical, surgical, radiologic, and immunotherapeutic care to cancer patients from across China. Sampling Patient participants were recruited using convenience, purposive sampling [ 16 ] to identify information-rich cases for in-depth study during 2022–2023. The eligibility criteria for this study were as follows: (I) adult patients with diagnosed cancer pathology; (II) cutaneous toxicity after immunotherapy; (III) normal listening, understanding, and communication skills; (III) knowledge of their condition and provided written informed consent to voluntarily participate in the study. The exclusion criteria for this study were as follows: (I) patients with other serious diseases; (II) cognitive dysfunction; (III) participation in other similar studies at the same time; (Ⅳ) judged to be not suitable to participate in the study. Seventeen patients participated in the study and completed a demographic form prior to the interviews (Table 1 ). The mean age of the participants was 53.78 years (standard deviation 10.00; range: 23–67 years). The mean number of years since diagnosis was 2.44 (standard deviation: 0.61; range: 1–3 years). Table 1 Demographic characteristics of the participants (n = 18). N Sex Age Diagnosis Immunotherapeutic Drugs Cycle Site Type Level N1 Male 60 Lung cancer Tislelizumab (PD1) 2 Lower extremities Maculopapular eruption 1 N2 Male 67 Lung cancer Camrelizumab (PD1) 1 Head RCCEP 1 N3 Male 56 Lung cancer Tislelizumab (PD1) 1 Hands, feet, scattered throughout the body Pruritus 1 N4 Female 58 Lung cancer Camrelizumab (PD1) 1 Head, neck, scattered throughout the body RCCEP 1 N5 Female 59 Thymic carcinoma Tislelizumab (PD1) 1 Hands, feet, scattered throughout the body Maculopapular eruption,pruritus 2 N6 Male 51 Lung cancer Camrelizumab (PD1) 2 Head, neck, scattered throughout the body RCCEP 1 N7 Male 53 Gastric cancer Sintilimab (PD1) 9 Hands, neck Vitiligo-like depigmentation 1 N8 Male 56 Gastric cancer Camrelizumab(PD1) 1 Head, neck, scattered throughout the body RCCEP 1 N9 Male 56 Nasopharyngeal carcinoma Camrelizumab (PD1) 4 Head, neck, scattered throughout the body RCCEP 1 N10 Male 49 Bowel cancer Sintilimab (PD1) 1 Head, neck, scattered throughout the body Pruritus, dermatitis 1 N11 Female 39 Lung cancer Tislelizumab (PD1) 2 Hands, feet Pruritus,dermatitis 2 N12 Male 61 Lung cancer Pembrolizumab(PD1) 4 Abdomen, back Maculopapular eruption,pruritus 2 N13 Female 58 Lung cancer Camrelizumab (PD1) 1 Head, neck, scattered throughout the body RCCEP,Acneiform eruptions 2 N14 Male 53 Esophageal carcinoma Pembrolizumab(PD1) 3 Calves Maculopapular eruption,pruritus 1 N15 Male 51 Lung cancer Tislelizumab (PD1) 3 Scattered throughout the body RCCEP 2 N16 Male 66 Hepatocarcinoma Tislelizumab (PD1) 8 Calves, scattered throughout the body Maculopapular eruption 2 N17 Male 23 Mediastinal cancer Toripalimab(PD1) 1 Scattered throughout the body Maculopapular eruption,pruritus 3 N18 Female 52 Gastric cancer Serplulimab (PD1) 1 Neck, arms, legs, scattered throughout the body Maculopapular eruption pruritus 3 RCCEP: Reactive cutaneous capillary endothelial proliferation. Data collection and analysis To achieve our study objectives, we designed a semi-structured interview utilizing the content analysis method, aiming to gather concise and targeted responses from the participants. The interview was developed including open-ended questions aim to collect their experience of immunotherapy-induced skin toxicity. The primary investigator (first author) of this study was a doctoral student, and the co-primary investigator was a master’s student. All investigators were female registered nurses with clinical experience in oncology care and training in systematic qualitative research methodologies. The face-to-face interviews were conducted individually by the primary investigator in a private room of the hospital, following a predetermined schedule. Each session lasted approximately 30 minutes. The primary investigator established an equal and trusting relationship with the interviewees prior to commencing the interviews. A comprehensive introduction was provided, including personal background of investigator, research objectives, and the methodology employed. Throughout the interview process, the first author maintained a neutral stance towards the participants’ responses, allowing them to freely express their personal experiences with cutaneous toxicity without any interference or interruption from the investigator or others [ 17 ]. The audio recordings were transcribed in Chinese by the primary investigator and then imported into the qualitative software analysis package NVivo 11.0. Transcripts of the interviews were independently coded by both the primary and co-primary investigators. Data analysis commenced after the initial interview and was conducted concurrently with data collection. Qualitative thematic analysis was employed to examine the qualitative data for significant statements and phrases. Colaizzi’s intensive and highly inductive approach [ 18 ] was utilized for data analysis, which involved the following: (i) multiple readings of the interview transcripts by the primary and co-primary investigators, while simultaneously listening to the audio recordings; (ii) identification of essential elements and meaningful statements from the audio recording transcripts; (iii) coding of these elements and statements; (iv) organization of the data into thematic clusters; (v) ensuring comprehensive descriptions were provided and merged for each theme; (vi) repeated review of the themes and descriptions by the investigators; and (vii) returning the data to the participants for verification. The sample size was determined by data saturation (i.e., when there was no further new information collected in relation to the emerging themes). After interviewing 18 patients, the investigators identified considerable repetition of data, which indicated data saturation; therefore, they terminated the data collection. Ethical considerations and clinical trial details The study received ethical approval from the Human Research Ethics Board at the research governance department of Nanfang Hospital, Guangzhou, China (approval number NFEC-2022-080). Prior to the interviews, all participants provided written informed consent; they were informed that their participation was voluntary, and they had the right to withdraw from the study at any stage. To maintain confidentiality, each patient was assigned a subject code, which was used for all interview transcripts and recordings. All audio recordings and documents were securely stored in a locked cabinet until the transcription process was completed. The accuracy of the transcripts was then verified by comparing them with the original recordings. The trial registration number was ChiCTR2200062265.The Study type was observational study. The data of registration was 31 July,2022. Results Three main themes were identified in the data: (i) management of skin toxicity in patients; (ii) patients’ experience of skin toxicity; and (iii) problems that skin toxicity poses for patients and the support they would like to receive. These themes are described in more detail below. Theme1 Management of Skin Toxicity in Patients Faced with the problem of skin toxicity after immunotherapy, patients managed their condition in different ways, such as seeking help from medical professionals, skin medication, bathing with care, d doing things to distract themselves from the problem, and traditional Chinese medicine. Find cutaneous toxicity problems Patients who noticed symptoms of skin toxicity often inquired about the cause of the symptoms via phone or WeChat. When the doctor explained that it is an adverse reaction to immunotherapy, the patient’s level of worry and fear was reduced. “I added doctor on WeChat (while I was at home). Once I asked him, he helped me and replied to me. If you get some positive answers from the doctors and nurses, you don’t have to be too worried about these adverse reactions that occur. There’s nothing to be afraid of because it’s mainly brought on by the treatment.” (N4) “I asked Dr. Wang and Dr. Sun. They said it was a normal reaction for capillaries to burst, so I’m not worried.” (N6) Applying Medication The patients often used moisturizers or topical ointments to relieve symptoms of itching or dryness. Some patients felt that these measures were effective in relieving symptoms; others considered topical medications or skin care products ineffective. “I have applied Qirixiang moisturizing cream, which is very comfortable. I applied moisturizer on it(skin) every night after my shower, so I didn’t feel itchy. But now it is cold, and it is not as effective as before.” (N5) “I took that ointment and applied it, but not every day, as it itches sometimes. Sometimes it itches, and after a while it doesn’t itch. It seems like using the ointment temporarily stops the itching. I don’t care about it(skin) when it stops itching.” (N9) “I would feel a little better after applying the urea ointment, just not as dry and itchy.” (N14) “At first, I thought it was too dry, wipe those dry is such as aloe vera cream ah. I also used dermatophyte, which is not effective, and it is more and more itchy. I also rubbed some (moisturizing skin care products),but with really no effect.” (N12) Be careful in the shower Patients reported that they needed to control the strength with which they cleaned their skin and pay extra attention to the temperature of the water when bathing. “Be careful when bathing; don’t rub hard with a towel. We should rub the skin with our hands slowly and gently.” (N2) “I usually don’t even care about it(RCCEP), mainly don’t scratch it and don’t tickle it. Pay attention when bathing; don’t rub it hard with a towel.” (N5) Distracting Attention In the face of the symptoms of distress, patients adopted self-adjustment strategies such as listening to music, talking, and other distractions. “I like listening to music and looking at my phone to distract myself.” (N5) "I also feel itchy, (but) because we’re talking, I'm distracted, which also has a controlling effect on the itching.” (N12) Using Traditional Chinese Medicine Some patients reported that when they perceived discomfort, they would relieve their symptoms through traditional Chinese medicine, such as boiling herbs in water for external or internal use, which promotes the metabolism of affected tissues. “The third time it(skin) was itchy, I think I went to the Chinese medicine department. The Chinese medicine practitioner gave me allergy medicine. I’ve taken a few packets of herbs. The Chinese medicine practitioner did not prescribe any kind of spray or compress medicine; most of them are oral, with some package like herbal tea.” (N1) “Using honeysuckle vine boiled in water to soak in a bath can be helpful in relieving red itchy symptoms. However, this method did not narrow the range of skin symptoms and did not cure them.” (N15) “At first, I used herbal water to rinse my whole body. Then the skin symptom areas scabbed over and I loosened the scabs by bathing.” (N16) Theme2 Patient Experience of Skin Toxicity Skin toxicity causes great physical and psychological distress for patients, affecting sleep, socialization, and other aspects of their lives. Obstacles in the treatment process such as recurring illnesses, lack of attention from doctors, and ineffective medications can erode a patient’s confidence. Influenced by various factors, such as the duress of disease symptoms, lack of knowledge about the disease, and worry about recovery from the disease, patients’ negative emotions (e.g., fear, distressed, hassle, helplessness, endurance, and boredom) increase. Impact of Skin Toxicity on Patients The interviews showed that the dramatic symptoms of cutaneous toxicity directly affected patients’ sleep, and may bring about changes in appearance and cause disturbances to patients’ normal lives to varying degrees. In addition, there are some potential risks of infection and bleeding. However, some patients say that they are more concerned about the effects of immunotherapy than the problems of skin toxicity. “Sometimes sleep is disturbed. If sleeping, you will wake up to scratch. I’m not particularly itchy during the day, just when I sleep, particularly when it’s hot.” (N3) “The pimple on this skin is nothing if you squeeze it out. It mainly affects me walking down the street, others would feel ugly with the pimple Even if I wear a mask, it’s easy for people to see my pimples.” (N15) “I’m inconvenienced in a lot of ways by having these (pimples) on my face, including the fact that I'm terrified of people seeing them when I go out to socialize. Also, I need to be gentler in the shower. As soon as I rub the lesions hard enough, they bleed. I’m coming to the hospital this time to get a prescription for something to stop the bleeding.” (N13) “I've got a splitting of my head. I feel like I have allergies all over my body, and my skin is swollen. I keep scratching my skin, and when I scratch, the skin gets redder and more swollen. The temperature of the red, swollen skin is higher than the normal skin. For example, I felt that the temperature of the skin in other parts of my body is 37 ℃, while the temperature of the skin in the red and swollen areas reached 40 ℃.” (N17) Positive View Most patients said that they focused more on the efficacy of the tumor treatment where the balance between immunotherapy effects and skin adverse reactions can achieve homeostasis based on the efficacy of treatment, and their expectations of the anti-tumor effects of immunotherapy outweighed the distress caused by the adverse skin reactions. Some patients had stronger physical and psychological tolerance, and thought that they could accept the effects of adverse reactions if the symptoms did not interfere with their normal lives. “I maintain good mentality. I think that is nothing; it is a normal reaction. I ignore it and don’t take it seriously every day.” (N2) “As long as it is effective, the problem of itchy skin can be tolerated; it’s fine.” (N3) “My only concern is not side effects; I am worried that this medicine has an effect on my tumor. I am afraid that it is resistant to the medicine; other side effects are completely solvable for me.” (N11) “There is no use for worrying about this now; the most important thing is to improve your situation.” (N15) Negative Emotions As immunotherapy progressed, the patients’ perceptions about their symptoms varied significantly. They suffered from different types of physical pain and began to show negative emotions, such as fearfulness, fatigue, troubled, and helpless. “If I was awake, I would control myself as much as possible to avoid scratching the rash. But if I fell asleep, I couldn't control myself from scratching the itchy skin, which made it easy to break the skin. The wound will become infected after being scratched, which is very scary.” (N12) “Being hospitalized was inconvenient. I was a little annoyed that I had to do nothing but eat, sleep, and get fluids every day.” (N18) “That’s what the doctor said; then you have to believe it, and there’s nothing you can do. If the doctors can’t do anything, what can we do?” (N8) “Do I have a choice? I only wait here. Anxiety is useless.” (N17) Theme3 Problems that Skin Toxicity Poses for Patients and the Support They Would Like to Receive Participants experiencing skin toxicity symptoms encountered some problems, such as recurrent symptoms and poor drug efficacy. Some patients did not take the symptoms of skin toxicity seriously enough or misunderstood them due to lack of information support. Many participants wanted healthcare professionals to take skin toxicity seriously and provide targeted solutions. Family members played an important role in assisting patients with applying for medicine and finding information. Problems Encountered Recurrent symptoms and poor medication efficacy caused some patients to become frustrated with their treatment. Patients with a lack of knowledge about skin toxicity may not pay sufficient attention to the symptoms of skin toxicity, and the symptoms are related to the oral administration of chemotherapy and sweating. At the same time, physician inattention affects the establishment of the patient-physician relationship and the patient’s evaluation of medical outcomes. “As soon as I used the immunotherapy, I would feel itchy after I went home. Most of the time, I feel itchy for three weeks after I do the treatment.” (N15) “I thought it was because I was sweating, so I felt itchy.” (N17) “I just found out about the rash on my body last Friday (a week before I was admitted to the hospital), and at first I thought it was related to the chemotherapy oral medication, and I was not sure about the relationship between the rash and the immunotherapy.” (N18) “I thought at first that the rash was due to the effect of this medicine on my disease. It’s a sign of skin toxicity, but I’m still willing to accept the adverse effects.” (N18) “We all know it’s the side effects of this drug, which we’ve figured out through each experience. No one even told us ahead of time what the adverse effects of immunotherapy would be. I didn’t ask around until I had symptoms.” (N13) “I told my doctor about my symptoms, but he probably never took them seriously. It wasn’t until the symptoms became worse that he told me to see the dermatologist.” (N15) “After telling the doctor, the hospital also prescribed medicine, but it didn’t work even after using it later. That medication prescribed by the doctor included both oral and external drugs to the skin , neither of which worked well, and I still felt itchy.” (N3) Hoping for More Support (from healthcare professionals) Most patients showed passive compliance with disease treatment; they hoped more for attention and guidance from healthcare professionals to be able to obtain accurate treatment information and targeted explanations, as well as participate in the decision-making of the treatment plan with the doctor. “I want the doctors and nurses to deal with my health issues. We don’t know the symptoms, and it’s left to the healthcare professionals to figure out how to fix them (symptoms).” (N12) “I definitely hope doctors and nurses pay attention to this issue.” (N16) “I wish doctors would ask their patients in detail if they are uncomfortable during their daily ward rounds. For example, doctors should routinely ask patients if they experience itching because some patients are not aware of the adverse effects themselves.” (N17) “I do have some doctor’s phone number. If I encounter problems, I will contact him. I wish the department would develop some online interventions. If I call the doctor at home, he can explain it to me quite carefully.” (N2) Assistance from Family Members Family members can help the patient apply their medication, especially in areas that are difficult to see, such as the back. In addition, younger family members are more familiar with the use of social networks, and they can search for relevant posts about experiences with skin toxicity, compare them with the patient’s symptoms, and make medication decisions accordingly. “My daughter mainly helps me with the application and spraying of medication, especially with the rash on my back where she needs to help. I take loratadine at home and apply glyburide lotion, also recommended by my daughter.” (N18) "My daughter helped me to look up how to deal with these skin symptoms online. My daughter said she mainly searched on Xiaohongshu (a social media platform), compared my symptoms with pictures of symptoms posted by others, and read experience posts shared by others that said taking loratadine was effective. I used to use this medicine when my family had allergies, and it worked well. I read the instructions and learned that there are no adverse reactions to this medicine, and I had this medicine at home and took it.” (N18) Discussion The interview results revealed that patients employ various strategies to manage skin toxicity, which can be categorized into two types. The first type involves proactive patients who reach out to doctors or nurses to seek information about the causes and treatment options for skin toxicity, which is a recommended approach. “Patient involvement” is not a new concept, but rather an extension and expansion of the “patient-centered” approach. Medical decision-making is the process of determining who needs what kind of medical intervention at what time [ 19 ], including decisions regarding examination, treatment, and care, and is the core component of medical activities. Thompson [ 20 ] argues that patient involvement in medical decision-making means patients participate in discussions about their own condition, provide their views on treatment, and are involved in the entire decision-making process. Coates et al. [ 21 ] propose that patient involvement in medical decision-making is the active process of patients asking questions and expressing their opinions and preferences to healthcare professionals. Degner et al. [ 22 ] believe that patient involvement in medical decision-making refers to the degree to which patients want to participate or have control in the decision-making process. Currently, in the context of patient-centered care models, patient involvement in medical decision-making has become a focus of research and a major challenge in clinical practice. Research has shown that patient involvement in medical decision-making can have a positive impact of patient outcomes [ 23 , 24 ]. Therefore, healthcare professionals should actively encourage patients to seek professional help after experiencing skin toxicity. Due to the delayed-onset nature of skin toxicity, most patients experience such toxicity while at home. However, the monitoring and provision of care by healthcare professionals during this period are insufficient, resulting in a lack of support for patients in their own homes. Some interviewees indicated that they relied on personal experience to manage symptoms. However, this approach carries the risk of inappropriate and untimely treatment. It is worth noting that immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and extended the survival of patients. ICIs, such as programmed death receptor 1 (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) monoclonal antibodies, provide targeted treatment with fewer side effects compared to conventional chemotherapeutic regimens. However, these advancements in treatment come at a high financial cost, with yearly ICI prices estimated to range from 50000–150000 USD for an individual [ 25 , 26 ]. These high medication costs can substantially add to patients’ financial burden [ 27 , 28 ]. The consensus is that financial toxicity will impact medication adherence in cancer treatment, including abandonment, delay, and discontinuation of treatment [ 29 , 30 ]. Cancer-related economic toxicity tends to cause negative emotions such as depression and anxiety, leading to a decrease in the motivation of cancer patients to acquire medical knowledge and seek medical help, which ultimately results in a lower quality of life [ 31 ]. These factors help to explain why some patients opt for self-management of skin toxicities, as they may have reservations about incurring extra expenses for treating side effects. Some of the interviewed patients had a positive attitude towards coping with skin toxicity, as they could rationally weigh the balance between treatment effectiveness and side effects. Their expectations for the anti-tumor effects of immunotherapy outweighed the troubles caused by adverse skin reactions. Compared with the side effects caused by adverse reactions, they prioritized treatment effectiveness. However, cancer is a highly distressing event that brings about physical and psychological pain and discomfort [ 32 ]. The impact of skin toxicity on patients is significant, as it affects them physically, psychologically, and economically. Various types of skin toxicity can result in physical symptoms. Excessive scratching may cause skin breakage and, in severe cases, scarring of the dermis. Persistent itching can lead to difficulties in concentration, severely disrupting the patient’s daily routine and reducing their quality of sleep. Skin toxicity affecting the oral mucosa can lead to reduced salivation and impaired taste, which greatly affects the patient’s ability to eat. Long-term reduced food intake can result in decreased nutritional levels and hinder recovery [ 8 ]. Reactive skin capillary endothelial hyperplasia is characterized by the formation of vascular nodules protruding from the skin’s surface. These nodules have thin walls that are prone to rupture, leading to bleeding and infection, causing significant discomfort to patients [ 33 ]. Vitiligo-like depigmentation is commonly observed in exposed areas of the skin [ 34 ], which requires patients to cover these areas when going outdoors to minimize light stimulation, further inconveniencing them [ 7 ]. Cancer patients often suffer from psychological distress, which not only affects their treatment and quality of life, but also is regarded as an independent risk factor for increased cancer mortality [ 35 ]. It is important to pay additional attention to patients who express negative emotions, as they may be experiencing fear, worry, helplessness, and other feelings, which are not conducive to coping with skin toxicity issues. Research has shown that patients are often concerned about poor skin prognosis and irreversible changes such as scarring [ 36 ]. In addition, skin eruptions, vascular nodules, vitiligo, and other changes in the appearance of the head and face hinder patients’ social interactions and further exacerbate their sense of shame. Stigma refers to an inner shame experience of patients with disease and is regarded as a negative psychological stress response [ 37 ]. One study showed that narrative nursing can reduce anxiety and depression in elderly patients with Bladder Cancer after ileal replacement of the bladder, as well as enhance their quality of life, reduce their stigma, and play a positive motivating role [ 38 ]. Therefore, such a nursing model should be promoted in clinical settings. The interview data shows that some patients had misconceptions about skin toxicity. Patients lacked awareness of the drugs used and their adverse reactions, which affected their coping effectiveness. One study suggested that educating patients before and during cancer treatment can deepen belief in the value of treatment, thereby enhancing treatment adherence and durability [ 39 ]. Disease awareness is an indicator that can be intervened. Targeted health knowledge education should be carried out for specific high-risk groups to improve their understanding of diseases, so as to improve patient participation in symptom management. As most patients are middle-aged or elderly, and skin toxicity occurs at home, they often rely on their family members for support. Therefore, it is essential to provide training for family members. Guidelines recommend that patients and their families receive timely health education from healthcare professionals about immune therapy, its mechanisms, and immune therapy–related adverse reactions before, during, and after treatment [ 13 ]. Nurses educating patients about immunotherapy can contribute to patient safety and improved outcomes [ 40 ]. The interview results indicated that patients did not receive timely responses from healthcare professionals when experiencing skin toxicity and hoped for more attention from them. This result reflects how, in the clinical environment, healthcare professionals do not pay sufficient attention to skin toxicity issues. Research has shown that the overall level of awareness of cancer immunotherapy among healthcare workers is low [ 41 ]. Healthcare professionals may not have sufficient knowledge about immune therapy–related adverse reactions, making it difficult for them to provide appropriate health education for patients. A European study showed that nurses had a high level of interest in learning about cancer immunotherapy and an overall positive attitude towards its use; furthermore, the need for nurses to be trained in immunotherapy was higher than that of oncologists and surgeons [ 42 ]. Nurses’ enthusiasm for learning about immunotherapy should be noted, as enhancing nurses’ knowledge of immunotherapy and developing effective skin toxicity management practices is imperative. Studies have proposed that immune therapy–related adverse reactions should be addressed through five stages: assessment, examination, diagnosis, treatment, and monitoring [ 15 ]. Early detection and prompt initiation of treatment may minimize severity and duration of symptoms, thereby improving quality of life and enabling patients to remain in treatment. As healthcare providers with high patient contact, nurses are often asked by patients to check their bodies or review skin pictures to explain the cause of the condition and advise on appropriate management. Nurses play an important role in the management of skin toxicity through early detection, health promotion, and coordination of treatment options with multiple departments. Current guidelines for the management of ICI toxicity are divided into organ categories, and practical guidelines based on clinical experience may be more helpful to healthcare workers in recognizing and managing skin toxicity [ 43 ]. Limitations This qualitative study only included results from patients with low-grade cutaneous toxicity, lacking analysis of data from patients with more severe cutaneous toxicity, which may have influenced the results to a certain extent. Additionally, it is possible that some interviews were conducted during either the acute phase or the recovery phase of cutaneous toxicity, which could also have influenced the responses. Conclusions This study highlights the experience of patients with cutaneous toxicity during immunotherapy. The measures taken and emotional reactions demonstrated during the process of experiencing cutaneous toxicity suggest that in future clinical practice, nurses should focus on enhancing patients’ awareness of immunotherapy and its adverse reactions. They should provide supportive measures to facilitate easier communication between patients and healthcare professionals, ensuring proper management of cutaneous toxicity issues. Declarations Author contribution statement Yang Zhao and Lili Zhang contributed to the study design, research setting contact, and part of the data acquisition. They contributed equally as corresponding authors. Zhihui Yang contributed to the conceptualization, methodology, and drafted the manuscript with input from all authors. Ruiqi Lu is the ‘joint first authorship for her contribution to this manuscript. Other authors have made different contributions to this study, including Investigation, data curation and formal analysis. All authors contributed to the interpretation of the results and approved the final manuscript. Acknowledgements The authors thank all the patients who participated in this study for their selfless sharing. Conflict of interest None. Funding sources This study was supported by the National Natural Science Foundation of China (grant agreement no.72204106. Data availability Statement All data generated or analyzed during this study are included in this published article. References Sung H, Ferlay J, Siegel RL, et al. (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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(2018) A systematic review of the cost and cost-effectiveness studies of immune checkpoint inhibitors. J Immunother Cancer 6(1):128. doi: 10.1186/s40425-018-0442-7 Zang S, Zhan H, Zhou L, Wang X (2019) “Research on Current Curative Expenditure among Lung Cancer Patients Based on the "System of Health Accounts 2011”: insights into influencing factors. J Cancer 10(26):6491–6501. doi: 10.7150/jca.34891 Chai Q, Shen Y, Du J, Zhu J, Wu B (2020) “Economic burden of patients with advanced non-small-cell lung cancer receiving nivolumab versus chemotherapy in China.” Immunotherapy vol. Immunotherapy 12(4):245–254. doi: 10.2217/imt-2020-0030 Abrams HR, Durbin S, Huang CX, et al. (2021) Financial toxicity in cancer care: origins, impact, and solutions. Transl Behav Med 11(11):2043–2054. doi: 10.1093/tbm/ibab091 Carrera PM, Kantarjian HM, Blinder VS (2018) The financial burden and distress of patients with cancer: understanding and stepping-up action on the financial toxicity of cancer treatment. CA Cancer J Clin 68(2):153–165. doi: 10.3322/caac.21443 Sun YL, Kuang Y, Yuan XY, et al. (2022) Survey on financial toxicity and its influencing factors in cancer survivors. J Nurs Sci 37(15):24–2731 Lai Q, Huang H, Zhu Y, et al. (2022 December) Incidence and risk factors for suicidal ideation in a sample of Chinese patients with mixed cancer types. Support Care Cancer 30(12):9811–9821. doi: 10.1007/s00520-022-07386-8 . PubMed: 36269433. PubMed Central: PMC9715447 Huang YX, Li X, Xiao M, et al. (2023) Camrelizumab causes reactive capillary hyperplasia. J Clin Dermatol 52(9):551–552 Larsabal M, Marti A, Jacquemin C, et al. (2017) Vitiligo-like lesions occurring in patients receiving anti-programmed cell death–1 therapies are clinically and biologically distinct from vitiligo. J Am Acad Dermatol 76(5):863–870. doi: 10.1016/j.jaad.2016.10.044 Yang YL, Liu L, Wang Y, et al. (2013) The prevalence of depression and anxiety among Chinese adults with cancer: A systematic review and meta-analysis. BMC Cancer 13:393. doi: 10.1186/1471-2407-13-393 Andersen ER, Eilertsen G, Myklebust AM, Eriksen S (2018) Women’s experience of acute cutaneous toxicity following radiation therapy in breast cancer. J Multidiscip Healthc 11:139–148. doi: 10.2147/JMDH.S155538 Andersen MM, Varga S, Folker AP (2022) On the definition of stigma. J Eval Clin Pract 28(5):847–853. doi: 10.1111/jep.13684 Wang L, Wu D, Wu S, et al. (2022) The effect of narrative nursing intervention on shame in elderly patients with bladder cancer after ileal bladder replacement: A cohort study. Comput Math Methods Med 2022:4299919. doi: 10.1155/2022/4299919 . Retraction in: Comput Math Methods Med (2023 September 27) 2023:9761783. doi:10.1155/2023/9761783, PubMed: 37799427. PubMed Central: PMC9262506 Puts MTE, Tu HA, Tourangeau A, et al. (2014) Factors influencing adherence to cancer treatment in older adults with cancer: a systematic review. Ann Oncol 25(3):564–577. doi: 10.1093/annonc/mdt433 Lasa-Blandon M, Stasi K, Hehir A, Fischer-Cartlidge E (2019) Patient education issues and strategies associated with immunotherapy. Semin Oncol Nurs 35(5):150933. doi: 10.1016/j.soncn.2019.08.012 Hamad RS (2020) Evaluation of awareness and understanding of cancer immunotherapy among healthcare professionals in eastern Saudi Arabia. J Oncol Pharm Pract 26(6):1343–1352. doi: 10.1177/1078155219891651 Mellstedt H, Gaudernack G, Gerritsen WR, et al. (2014) Awareness and understanding of cancer immunotherapy in Europe. Hum Vaccin Immunother 10(7):1828–1835. doi: 10.4161/hv.28943 Thebeau M, Rubin K, Hofmann M, Grimm J, Weinstein A, Choi JN (2017) Management of skin adverse events associated with immune checkpoint inhibitors in patients with melanoma: A nursing perspective. J Am Assoc Nurse Pract 29(5):294–303. doi: 10.1002/2327-6924.12458 . PubMed: 28436601 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3899394","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":270162137,"identity":"3255a6bc-10c3-4345-ab62-68b112802d6c","order_by":0,"name":"Zhihui Yang","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhihui","middleName":"","lastName":"Yang","suffix":""},{"id":270162138,"identity":"39bc9fcc-6ac4-429e-a5ca-76ecc431e252","order_by":1,"name":"Ruiqi Lu","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ruiqi","middleName":"","lastName":"Lu","suffix":""},{"id":270162139,"identity":"39b0185c-27b2-4622-ae73-ba90556206d9","order_by":2,"name":"Xingwen Li","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xingwen","middleName":"","lastName":"Li","suffix":""},{"id":270162140,"identity":"e5abac5c-2c91-4be4-8afb-71bc1c45aeca","order_by":3,"name":"Suting Liu","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Suting","middleName":"","lastName":"Liu","suffix":""},{"id":270162141,"identity":"e362ee10-a388-4113-9a59-a142159947ee","order_by":4,"name":"Yuanyuan Luo","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuanyuan","middleName":"","lastName":"Luo","suffix":""},{"id":270162142,"identity":"d5209692-456f-4e5f-8ec2-b02510f8bc06","order_by":5,"name":"Ziqi Wang","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ziqi","middleName":"","lastName":"Wang","suffix":""},{"id":270162143,"identity":"92697eaa-199a-4b3f-9dcd-bfe46fd3cefc","order_by":6,"name":"Yang Zhao","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Zhao","suffix":""},{"id":270162144,"identity":"a8519fce-c9fb-458e-94f4-46ac47a2e732","order_by":7,"name":"Lili Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIiWNgGAWjYDACCRBRICHDBuXLsbG3HyBCi4EED0yLMR/PmQRitDDwwPiJ8yQcDPDqkJ/d/OzhFwMLHj4G9ssff+YcTm+TYEhg+FGxDacWxjnHzI1lwA7jKTDm3XY4t0268QBjz5nbOLUwSySYSUtAtCQkM4K0yBxIYGZsw62FTSL9G1zLwZ/bDqezSSQY4NXCI5FjJvkBrIX9YAPQYQkEtUhI5JRJQwKZh5mZd1u6YRswkA/i84v8jPRtkj8q6uTkG9gff/y5zVpevr394IMfFbi1gIMAHCnybxDRcQCveiBg/AGm2B8QUjgKRsEoGAUjFAAA2UtKuVpyxCoAAAAASUVORK5CYII=","orcid":"","institution":"Southern Medical University","correspondingAuthor":true,"prefix":"","firstName":"Lili","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-01-26 08:16:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3899394/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3899394/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58837211,"identity":"d801fcbb-15e1-4636-b011-ce6500394981","added_by":"auto","created_at":"2024-06-21 20:22:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":610610,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3899394/v1/f12d59fb-ff42-40a7-960a-57b38eacb2ae.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Experiences of immune-related skin toxicity: a qualitative study among patients with cancer","fulltext":[{"header":"Background","content":"\u003cp\u003eAccording to Global Cancer Statistics, there has been a rapid increase in the incidence and mortality rate of cancer worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In 2022, approximately 4.82\u0026nbsp;million new cancer cases were recorded in China [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Among numerous immunotherapeutic strategies, immune checkpoint blockade has shown remarkable benefits in the treatment of different types of cancer. In recent years, immune checkpoint inhibitors have emerged as a promising antitumor therapy following surgery, radiotherapy, chemotherapy, and targeted therapy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. These inhibitors have revolutionized cancer treatment, providing a positive response for 25% of patients. Currently, immune checkpoint inhibitors are approved by the US Food and Drug Administration for treatment of eight types of cancer [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eImmune checkpoint inhibitors have distinct mechanisms of action compared to standard anticancer therapies. By increasing the activity of the immune system, immune checkpoint blockade can induce inflammatory side-effects termed immune-related adverse events. The gastrointestinal tract, endocrine glands, skin, and liver are the organ systems most affected by these adverse events [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Aside from their impact on patients\u0026rsquo; quality of life, severe cases of immune-related adverse events can lead to a reduction or discontinuation of antitumor medications, affecting the progress of treatment [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Immune-related cutaneous adverse events are an early form of immune-related adverse events, which include pruritus, rash, and reactivity skin capillary endotheliosis, oral mucosal lichenoid reaction and Sj\u0026ouml;gren\u0026rsquo;s syndrome, bullous pemphigoid, vitiligo, and Stevens\u0026ndash;Johnson syndrome [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In one study, the incidence of immune-related cutaneous adverse events was 43\u0026ndash;45% in patients treated with CTLA-4 inhibitors and approximately 18\u0026ndash;23% in patients treated with PD-1 inhibitors [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The median time to onset varies among the various types of skin toxicity, with most symptoms appearing early during treatment [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Skin toxicity occurs on average 3\u0026ndash;4 weeks after the start of treatment [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Most cutaneous toxicity reactions are classified as grades 1\u0026ndash;2, whereas adverse events of grades 3\u0026ndash;4 are rarely reported. Severe cutaneous adverse events are less common but are important to recognize and treat promptly [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Patients experiencing skin toxicity can become annoyed and frustrated; severe skin toxicity can cause patients to worry about the long-term effects of immunotherapy, and skin discomfort may limit their activities [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Furthermore, patients often must return to the hospital for examination or treatment due to adverse skin events, increasing the cost and burden of their treatment [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The current research mainly focuses on exploring the incidence and influencing factors of adverse reactions, and there are also some qualitative studies on patient experiences. However, there are limited qualitative studies focusing on the patient experience of immune-related skin toxicity. Since skin toxicity is the most common adverse event, gaining a deeper understanding of patients' perspectives is of great significance for subsequent symptom management.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDesign and setting\u003c/h2\u003e \u003cp\u003eA qualitative descriptive design was utilized in this study, which took place at a comprehensive cancer treatment facility in Southern China. The hospital is renowned for its expertise in providing medical, surgical, radiologic, and immunotherapeutic care to cancer patients from across China.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSampling\u003c/h2\u003e \u003cp\u003ePatient participants were recruited using convenience, purposive sampling [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] to identify information-rich cases for in-depth study during 2022\u0026ndash;2023. The eligibility criteria for this study were as follows: (I) adult patients with diagnosed cancer pathology; (II) cutaneous toxicity after immunotherapy; (III) normal listening, understanding, and communication skills; (III) knowledge of their condition and provided written informed consent to voluntarily participate in the study. The exclusion criteria for this study were as follows: (I) patients with other serious diseases; (II) cognitive dysfunction; (III) participation in other similar studies at the same time; (Ⅳ) judged to be not suitable to participate in the study. Seventeen patients participated in the study and completed a demographic form prior to the interviews (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean age of the participants was 53.78 years (standard deviation 10.00; range: 23\u0026ndash;67 years). The mean number of years since diagnosis was 2.44 (standard deviation: 0.61; range: 1\u0026ndash;3 years).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics of the participants (n\u0026thinsp;=\u0026thinsp;18).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eImmunotherapeutic Drugs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCycle\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSite\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eType\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTislelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLower extremities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMaculopapular eruption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCamrelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHead\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRCCEP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTislelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHands, feet, scattered throughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePruritus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCamrelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 \u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHead, neck, scattered \u003c/p\u003e \u003cp\u003ethroughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRCCEP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThymic\u003c/p\u003e \u003cp\u003ecarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTislelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHands, feet, scattered \u003c/p\u003e \u003cp\u003ethroughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMaculopapular eruption,pruritus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCamrelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHead, neck, scattered\u003c/p\u003e \u003cp\u003e throughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRCCEP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGastric cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSintilimab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHands, neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eVitiligo-like depigmentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGastric cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCamrelizumab(PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHead, neck, scattered \u003c/p\u003e \u003cp\u003ethroughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRCCEP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNasopharyngeal\u003c/p\u003e \u003cp\u003e carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCamrelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHead, neck, scattered \u003c/p\u003e \u003cp\u003ethroughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRCCEP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBowel cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSintilimab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHead, neck, scattered \u003c/p\u003e \u003cp\u003ethroughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePruritus,\u003c/p\u003e \u003cp\u003edermatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTislelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHands, feet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePruritus,dermatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePembrolizumab(PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAbdomen, back\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMaculopapular eruption,pruritus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCamrelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHead, neck, scattered\u003c/p\u003e \u003cp\u003e throughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRCCEP,Acneiform eruptions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEsophageal\u003c/p\u003e \u003cp\u003ecarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePembrolizumab(PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCalves\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMaculopapular eruption,pruritus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTislelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eScattered throughout \u003c/p\u003e \u003cp\u003ethe body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRCCEP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHepatocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTislelizumab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCalves, scattered \u003c/p\u003e \u003cp\u003ethroughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMaculopapular eruption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMediastinal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eToripalimab(PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eScattered throughout\u003c/p\u003e \u003cp\u003e the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMaculopapular eruption,pruritus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGastric cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSerplulimab (PD1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNeck, arms, legs, scattered throughout the body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMaculopapular eruption pruritus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRCCEP: Reactive cutaneous capillary endothelial proliferation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData collection and analysis\u003c/h2\u003e \u003cp\u003eTo achieve our study objectives, we designed a semi-structured interview utilizing the content analysis method, aiming to gather concise and targeted responses from the participants. The interview was developed including open-ended questions aim to collect their experience of immunotherapy-induced skin toxicity.\u003c/p\u003e \u003cp\u003eThe primary investigator (first author) of this study was a doctoral student, and the co-primary investigator was a master\u0026rsquo;s student. All investigators were female registered nurses with clinical experience in oncology care and training in systematic qualitative research methodologies. The face-to-face interviews were conducted individually by the primary investigator in a private room of the hospital, following a predetermined schedule. Each session lasted approximately 30 minutes.\u003c/p\u003e \u003cp\u003eThe primary investigator established an equal and trusting relationship with the interviewees prior to commencing the interviews. A comprehensive introduction was provided, including personal background of investigator, research objectives, and the methodology employed. Throughout the interview process, the first author maintained a neutral stance towards the participants\u0026rsquo; responses, allowing them to freely express their personal experiences with cutaneous toxicity without any interference or interruption from the investigator or others [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The audio recordings were transcribed in Chinese by the primary investigator and then imported into the qualitative software analysis package NVivo 11.0. Transcripts of the interviews were independently coded by both the primary and co-primary investigators.\u003c/p\u003e \u003cp\u003eData analysis commenced after the initial interview and was conducted concurrently with data collection. Qualitative thematic analysis was employed to examine the qualitative data for significant statements and phrases. Colaizzi\u0026rsquo;s intensive and highly inductive approach [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] was utilized for data analysis, which involved the following: (i) multiple readings of the interview transcripts by the primary and co-primary investigators, while simultaneously listening to the audio recordings; (ii) identification of essential elements and meaningful statements from the audio recording transcripts; (iii) coding of these elements and statements; (iv) organization of the data into thematic clusters; (v) ensuring comprehensive descriptions were provided and merged for each theme; (vi) repeated review of the themes and descriptions by the investigators; and (vii) returning the data to the participants for verification.\u003c/p\u003e \u003cp\u003eThe sample size was determined by data saturation (i.e., when there was no further new information collected in relation to the emerging themes). After interviewing 18 patients, the investigators identified considerable repetition of data, which indicated data saturation; therefore, they terminated the data collection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eEthical considerations and clinical trial details\u003c/h2\u003e \u003cp\u003e The study received ethical approval from the Human Research Ethics Board at the research governance department of Nanfang Hospital, Guangzhou, China (approval number NFEC-2022-080). Prior to the interviews, all participants provided written informed consent; they were informed that their participation was voluntary, and they had the right to withdraw from the study at any stage. To maintain confidentiality, each patient was assigned a subject code, which was used for all interview transcripts and recordings. All audio recordings and documents were securely stored in a locked cabinet until the transcription process was completed. The accuracy of the transcripts was then verified by comparing them with the original recordings. The trial registration number was ChiCTR2200062265.The Study type was observational study. The data of registration was 31 July,2022.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThree main themes were identified in the data: (i) management of skin toxicity in patients; (ii) patients\u0026rsquo; experience of skin toxicity; and (iii) problems that skin toxicity poses for patients and the support they would like to receive. These themes are described in more detail below.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTheme1 Management of Skin Toxicity in Patients\u003c/h2\u003e \u003cp\u003eFaced with the problem of skin toxicity after immunotherapy, patients managed their condition in different ways, such as seeking help from medical professionals, skin medication, bathing with care, d doing things to distract themselves from the problem, and traditional Chinese medicine.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eFind cutaneous toxicity problems\u003c/h2\u003e \u003cp\u003ePatients who noticed symptoms of skin toxicity often inquired about the cause of the symptoms via phone or WeChat. When the doctor explained that it is an adverse reaction to immunotherapy, the patient\u0026rsquo;s level of worry and fear was reduced.\u003c/p\u003e \u003cp\u003e\u0026ldquo;I added doctor on WeChat (while I was at home). Once I asked him, he helped me and replied to me. If you get some positive answers from the doctors and nurses, you don\u0026rsquo;t have to be too worried about these adverse reactions that occur. There\u0026rsquo;s nothing to be afraid of because it\u0026rsquo;s mainly brought on by the treatment.\u0026rdquo; (N4)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I asked Dr. Wang and Dr. Sun. They said it was a normal reaction for capillaries to burst, so I\u0026rsquo;m not worried.\u0026rdquo; (N6)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eApplying Medication\u003c/h2\u003e \u003cp\u003eThe patients often used moisturizers or topical ointments to relieve symptoms of itching or dryness. Some patients felt that these measures were effective in relieving symptoms; others considered topical medications or skin care products ineffective.\u003c/p\u003e \u003cp\u003e\u0026ldquo;I have applied Qirixiang moisturizing cream, which is very comfortable. I applied moisturizer on it(skin) every night after my shower, so I didn\u0026rsquo;t feel itchy. But now it is cold, and it is not as effective as before.\u0026rdquo; (N5)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I took that ointment and applied it, but not every day, as it itches sometimes. Sometimes it itches, and after a while it doesn\u0026rsquo;t itch. It seems like using the ointment temporarily stops the itching. I don\u0026rsquo;t care about it(skin) when it stops itching.\u0026rdquo; (N9)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I would feel a little better after applying the urea ointment, just not as dry and itchy.\u0026rdquo; (N14)\u003c/p\u003e \u003cp\u003e\u0026ldquo;At first, I thought it was too dry, wipe those dry is such as aloe vera cream ah. I also used dermatophyte, which is not effective, and it is more and more itchy. I also rubbed some (moisturizing skin care products),but with really no effect.\u0026rdquo; (N12)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eBe careful in the shower\u003c/h2\u003e \u003cp\u003ePatients reported that they needed to control the strength with which they cleaned their skin and pay extra attention to the temperature of the water when bathing.\u003c/p\u003e \u003cp\u003e\u0026ldquo;Be careful when bathing; don\u0026rsquo;t rub hard with a towel. We should rub the skin with our hands slowly and gently.\u0026rdquo; (N2)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I usually don\u0026rsquo;t even care about it(RCCEP), mainly don\u0026rsquo;t scratch it and don\u0026rsquo;t tickle it. Pay attention when bathing; don\u0026rsquo;t rub it hard with a towel.\u0026rdquo; (N5)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDistracting Attention\u003c/h2\u003e \u003cp\u003eIn the face of the symptoms of distress, patients adopted self-adjustment strategies such as listening to music, talking, and other distractions.\u003c/p\u003e \u003cp\u003e\u0026ldquo;I like listening to music and looking at my phone to distract myself.\u0026rdquo; (N5)\u003c/p\u003e \u003cp\u003e\"I also feel itchy, (but) because we\u0026rsquo;re talking, I'm distracted, which also has a controlling effect on the itching.\u0026rdquo; (N12)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eUsing Traditional Chinese Medicine\u003c/h2\u003e \u003cp\u003eSome patients reported that when they perceived discomfort, they would relieve their symptoms through traditional Chinese medicine, such as boiling herbs in water for external or internal use, which promotes the metabolism of affected tissues.\u003c/p\u003e \u003cp\u003e\u0026ldquo;The third time it(skin) was itchy, I think I went to the Chinese medicine department. The Chinese medicine practitioner gave me allergy medicine. I\u0026rsquo;ve taken a few packets of herbs. The Chinese medicine practitioner did not prescribe any kind of spray or compress medicine; most of them are oral, with some package like herbal tea.\u0026rdquo; (N1)\u003c/p\u003e \u003cp\u003e\u0026ldquo;Using honeysuckle vine boiled in water to soak in a bath can be helpful in relieving red itchy symptoms. However, this method did not narrow the range of skin symptoms and did not cure them.\u0026rdquo; (N15)\u003c/p\u003e \u003cp\u003e\u0026ldquo;At first, I used herbal water to rinse my whole body. Then the skin symptom areas scabbed over and I loosened the scabs by bathing.\u0026rdquo; (N16)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eTheme2 Patient Experience of Skin Toxicity\u003c/h2\u003e \u003cp\u003eSkin toxicity causes great physical and psychological distress for patients, affecting sleep, socialization, and other aspects of their lives. Obstacles in the treatment process such as recurring illnesses, lack of attention from doctors, and ineffective medications can erode a patient\u0026rsquo;s confidence. Influenced by various factors, such as the duress of disease symptoms, lack of knowledge about the disease, and worry about recovery from the disease, patients\u0026rsquo; negative emotions (e.g., fear, distressed, hassle, helplessness, endurance, and boredom) increase.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eImpact of Skin Toxicity on Patients\u003c/h2\u003e \u003cp\u003eThe interviews showed that the dramatic symptoms of cutaneous toxicity directly affected patients\u0026rsquo; sleep, and may bring about changes in appearance and cause disturbances to patients\u0026rsquo; normal lives to varying degrees. In addition, there are some potential risks of infection and bleeding. However, some patients say that they are more concerned about the effects of immunotherapy than the problems of skin toxicity.\u003c/p\u003e \u003cp\u003e\u0026ldquo;Sometimes sleep is disturbed. If sleeping, you will wake up to scratch. I\u0026rsquo;m not particularly itchy during the day, just when I sleep, particularly when it\u0026rsquo;s hot.\u0026rdquo; (N3)\u003c/p\u003e \u003cp\u003e\u0026ldquo;The pimple on this skin is nothing if you squeeze it out. It mainly affects me walking down the street, others would feel ugly with the pimple Even if I wear a mask, it\u0026rsquo;s easy for people to see my pimples.\u0026rdquo; (N15)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I\u0026rsquo;m inconvenienced in a lot of ways by having these (pimples) on my face, including the fact that I'm terrified of people seeing them when I go out to socialize. Also, I need to be gentler in the shower. As soon as I rub the lesions hard enough, they bleed. I\u0026rsquo;m coming to the hospital this time to get a prescription for something to stop the bleeding.\u0026rdquo; (N13)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I've got a splitting of my head. I feel like I have allergies all over my body, and my skin is swollen. I keep scratching my skin, and when I scratch, the skin gets redder and more swollen. The temperature of the red, swollen skin is higher than the normal skin. For example, I felt that the temperature of the skin in other parts of my body is 37 ℃, while the temperature of the skin in the red and swollen areas reached 40 ℃.\u0026rdquo; (N17)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003ePositive View\u003c/h2\u003e \u003cp\u003eMost patients said that they focused more on the efficacy of the tumor treatment where the balance between immunotherapy effects and skin adverse reactions can achieve homeostasis based on the efficacy of treatment, and their expectations of the anti-tumor effects of immunotherapy outweighed the distress caused by the adverse skin reactions. Some patients had stronger physical and psychological tolerance, and thought that they could accept the effects of adverse reactions if the symptoms did not interfere with their normal lives.\u003c/p\u003e \u003cp\u003e\u0026ldquo;I maintain good mentality. I think that is nothing; it is a normal reaction. I ignore it and don\u0026rsquo;t take it seriously every day.\u0026rdquo; (N2)\u003c/p\u003e \u003cp\u003e\u0026ldquo;As long as it is effective, the problem of itchy skin can be tolerated; it\u0026rsquo;s fine.\u0026rdquo; (N3)\u003c/p\u003e \u003cp\u003e\u0026ldquo;My only concern is not side effects; I am worried that this medicine has an effect on my tumor. I am afraid that it is resistant to the medicine; other side effects are completely solvable for me.\u0026rdquo; (N11)\u003c/p\u003e \u003cp\u003e\u0026ldquo;There is no use for worrying about this now; the most important thing is to improve your situation.\u0026rdquo; (N15)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eNegative Emotions\u003c/h2\u003e \u003cp\u003eAs immunotherapy progressed, the patients\u0026rsquo; perceptions about their symptoms varied significantly. They suffered from different types of physical pain and began to show negative emotions, such as fearfulness, fatigue, troubled, and helpless.\u003c/p\u003e \u003cp\u003e\u0026ldquo;If I was awake, I would control myself as much as possible to avoid scratching the rash. But if I fell asleep, I couldn't control myself from scratching the itchy skin, which made it easy to break the skin. The wound will become infected after being scratched, which is very scary.\u0026rdquo; (N12)\u003c/p\u003e \u003cp\u003e\u0026ldquo;Being hospitalized was inconvenient. I was a little annoyed that I had to do nothing but eat, sleep, and get fluids every day.\u0026rdquo; (N18)\u003c/p\u003e \u003cp\u003e\u0026ldquo;That\u0026rsquo;s what the doctor said; then you have to believe it, and there\u0026rsquo;s nothing you can do. If the doctors can\u0026rsquo;t do anything, what can we do?\u0026rdquo; (N8)\u003c/p\u003e \u003cp\u003e\u0026ldquo;Do I have a choice? I only wait here. Anxiety is useless.\u0026rdquo; (N17)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eTheme3 Problems that Skin Toxicity Poses for Patients and the Support\u003c/h2\u003e \u003cp\u003eThey Would Like to Receive Participants experiencing skin toxicity symptoms encountered some problems, such as recurrent symptoms and poor drug efficacy. Some patients did not take the symptoms of skin toxicity seriously enough or misunderstood them due to lack of information support. Many participants wanted healthcare professionals to take skin toxicity seriously and provide targeted solutions. Family members played an important role in assisting patients with applying for medicine and finding information.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eProblems Encountered\u003c/h2\u003e \u003cp\u003eRecurrent symptoms and poor medication efficacy caused some patients to become frustrated with their treatment. Patients with a lack of knowledge about skin toxicity may not pay sufficient attention to the symptoms of skin toxicity, and the symptoms are related to the oral administration of chemotherapy and sweating. At the same time, physician inattention affects the establishment of the patient-physician relationship and the patient\u0026rsquo;s evaluation of medical outcomes.\u003c/p\u003e \u003cp\u003e\u0026ldquo;As soon as I used the immunotherapy, I would feel itchy after I went home. Most of the time, I feel itchy for three weeks after I do the treatment.\u0026rdquo; (N15)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I thought it was because I was sweating, so I felt itchy.\u0026rdquo; (N17)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I just found out about the rash on my body last Friday (a week before I was admitted to the hospital), and at first I thought it was related to the chemotherapy oral medication, and I was not sure about the relationship between the rash and the immunotherapy.\u0026rdquo; (N18)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I thought at first that the rash was due to the effect of this medicine on my disease. It\u0026rsquo;s a sign of skin toxicity, but I\u0026rsquo;m still willing to accept the adverse effects.\u0026rdquo; (N18)\u003c/p\u003e \u003cp\u003e\u0026ldquo;We all know it\u0026rsquo;s the side effects of this drug, which we\u0026rsquo;ve figured out through each experience. No one even told us ahead of time what the adverse effects of immunotherapy would be. I didn\u0026rsquo;t ask around until I had symptoms.\u0026rdquo; (N13)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I told my doctor about my symptoms, but he probably never took them seriously. It wasn\u0026rsquo;t until the symptoms became worse that he told me to see the dermatologist.\u0026rdquo; (N15)\u003c/p\u003e \u003cp\u003e\u0026ldquo;After telling the doctor, the hospital also prescribed medicine, but it didn\u0026rsquo;t work even after using it later. That medication prescribed by the doctor included both oral and external drugs to the skin\u003c/p\u003e \u003cp\u003e, neither of which worked well, and I still felt itchy.\u0026rdquo; (N3)\u003c/p\u003e \u003cp\u003eHoping for More Support (from healthcare professionals)\u003c/p\u003e \u003cp\u003eMost patients showed passive compliance with disease treatment; they hoped more for attention and guidance from healthcare professionals to be able to obtain accurate treatment information and targeted explanations, as well as participate in the decision-making of the treatment plan with the doctor.\u003c/p\u003e \u003cp\u003e\u0026ldquo;I want the doctors and nurses to deal with my health issues. We don\u0026rsquo;t know the symptoms, and it\u0026rsquo;s left to the healthcare professionals to figure out how to fix them (symptoms).\u0026rdquo; (N12)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I definitely hope doctors and nurses pay attention to this issue.\u0026rdquo; (N16)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I wish doctors would ask their patients in detail if they are uncomfortable during their daily ward rounds. For example, doctors should routinely ask patients if they experience itching because some patients are not aware of the adverse effects themselves.\u0026rdquo; (N17)\u003c/p\u003e \u003cp\u003e\u0026ldquo;I do have some doctor\u0026rsquo;s phone number. If I encounter problems, I will contact him. I wish the department would develop some online interventions. If I call the doctor at home, he can explain it to me quite carefully.\u0026rdquo; (N2)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eAssistance from Family Members\u003c/h2\u003e \u003cp\u003eFamily members can help the patient apply their medication, especially in areas that are difficult to see, such as the back. In addition, younger family members are more familiar with the use of social networks, and they can search for relevant posts about experiences with skin toxicity, compare them with the patient\u0026rsquo;s symptoms, and make medication decisions accordingly.\u003c/p\u003e \u003cp\u003e\u0026ldquo;My daughter mainly helps me with the application and spraying of medication, especially with the rash on my back where she needs to help. I take loratadine at home and apply glyburide lotion, also recommended by my daughter.\u0026rdquo; (N18)\u003c/p\u003e \u003cp\u003e\"My daughter helped me to look up how to deal with these skin symptoms online. My daughter said she mainly searched on Xiaohongshu (a social media platform), compared my symptoms with pictures of symptoms posted by others, and read experience posts shared by others that said taking loratadine was effective. I used to use this medicine when my family had allergies, and it worked well. I read the instructions and learned that there are no adverse reactions to this medicine, and I had this medicine at home and took it.\u0026rdquo; (N18)\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe interview results revealed that patients employ various strategies to manage skin toxicity, which can be categorized into two types. The first type involves proactive patients who reach out to doctors or nurses to seek information about the causes and treatment options for skin toxicity, which is a recommended approach. \u0026ldquo;Patient involvement\u0026rdquo; is not a new concept, but rather an extension and expansion of the \u0026ldquo;patient-centered\u0026rdquo; approach. Medical decision-making is the process of determining who needs what kind of medical intervention at what time [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], including decisions regarding examination, treatment, and care, and is the core component of medical activities. Thompson [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] argues that patient involvement in medical decision-making means patients participate in discussions about their own condition, provide their views on treatment, and are involved in the entire decision-making process. Coates et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] propose that patient involvement in medical decision-making is the active process of patients asking questions and expressing their opinions and preferences to healthcare professionals. Degner et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] believe that patient involvement in medical decision-making refers to the degree to which patients want to participate or have control in the decision-making process. Currently, in the context of patient-centered care models, patient involvement in medical decision-making has become a focus of research and a major challenge in clinical practice. Research has shown that patient involvement in medical decision-making can have a positive impact of patient outcomes [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Therefore, healthcare professionals should actively encourage patients to seek professional help after experiencing skin toxicity.\u003c/p\u003e \u003cp\u003eDue to the delayed-onset nature of skin toxicity, most patients experience such toxicity while at home. However, the monitoring and provision of care by healthcare professionals during this period are insufficient, resulting in a lack of support for patients in their own homes. Some interviewees indicated that they relied on personal experience to manage symptoms. However, this approach carries the risk of inappropriate and untimely treatment. It is worth noting that immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and extended the survival of patients. ICIs, such as programmed death receptor 1 (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) monoclonal antibodies, provide targeted treatment with fewer side effects compared to conventional chemotherapeutic regimens. However, these advancements in treatment come at a high financial cost, with yearly ICI prices estimated to range from 50000\u0026ndash;150000 USD for an individual [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. These high medication costs can substantially add to patients\u0026rsquo; financial burden [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The consensus is that financial toxicity will impact medication adherence in cancer treatment, including abandonment, delay, and discontinuation of treatment [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Cancer-related economic toxicity tends to cause negative emotions such as depression and anxiety, leading to a decrease in the motivation of cancer patients to acquire medical knowledge and seek medical help, which ultimately results in a lower quality of life [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. These factors help to explain why some patients opt for self-management of skin toxicities, as they may have reservations about incurring extra expenses for treating side effects.\u003c/p\u003e \u003cp\u003eSome of the interviewed patients had a positive attitude towards coping with skin toxicity, as they could rationally weigh the balance between treatment effectiveness and side effects. Their expectations for the anti-tumor effects of immunotherapy outweighed the troubles caused by adverse skin reactions. Compared with the side effects caused by adverse reactions, they prioritized treatment effectiveness.\u003c/p\u003e \u003cp\u003eHowever, cancer is a highly distressing event that brings about physical and psychological pain and discomfort [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The impact of skin toxicity on patients is significant, as it affects them physically, psychologically, and economically. Various types of skin toxicity can result in physical symptoms. Excessive scratching may cause skin breakage and, in severe cases, scarring of the dermis. Persistent itching can lead to difficulties in concentration, severely disrupting the patient\u0026rsquo;s daily routine and reducing their quality of sleep. Skin toxicity affecting the oral mucosa can lead to reduced salivation and impaired taste, which greatly affects the patient\u0026rsquo;s ability to eat. Long-term reduced food intake can result in decreased nutritional levels and hinder recovery [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Reactive skin capillary endothelial hyperplasia is characterized by the formation of vascular nodules protruding from the skin\u0026rsquo;s surface. These nodules have thin walls that are prone to rupture, leading to bleeding and infection, causing significant discomfort to patients [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Vitiligo-like depigmentation is commonly observed in exposed areas of the skin [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], which requires patients to cover these areas when going outdoors to minimize light stimulation, further inconveniencing them [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCancer patients often suffer from psychological distress, which not only affects their treatment and quality of life, but also is regarded as an independent risk factor for increased cancer mortality [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. It is important to pay additional attention to patients who express negative emotions, as they may be experiencing fear, worry, helplessness, and other feelings, which are not conducive to coping with skin toxicity issues. Research has shown that patients are often concerned about poor skin prognosis and irreversible changes such as scarring [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In addition, skin eruptions, vascular nodules, vitiligo, and other changes in the appearance of the head and face hinder patients\u0026rsquo; social interactions and further exacerbate their sense of shame. Stigma refers to an inner shame experience of patients with disease and is regarded as a negative psychological stress response [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. One study showed that narrative nursing can reduce anxiety and depression in elderly patients with Bladder Cancer after ileal replacement of the bladder, as well as enhance their quality of life, reduce their stigma, and play a positive motivating role [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Therefore, such a nursing model should be promoted in clinical settings.\u003c/p\u003e \u003cp\u003eThe interview data shows that some patients had misconceptions about skin toxicity. Patients lacked awareness of the drugs used and their adverse reactions, which affected their coping effectiveness. One study suggested that educating patients before and during cancer treatment can deepen belief in the value of treatment, thereby enhancing treatment adherence and durability [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Disease awareness is an indicator that can be intervened. Targeted health knowledge education should be carried out for specific high-risk groups to improve their understanding of diseases, so as to improve patient participation in symptom management. As most patients are middle-aged or elderly, and skin toxicity occurs at home, they often rely on their family members for support. Therefore, it is essential to provide training for family members. Guidelines recommend that patients and their families receive timely health education from healthcare professionals about immune therapy, its mechanisms, and immune therapy\u0026ndash;related adverse reactions before, during, and after treatment [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Nurses educating patients about immunotherapy can contribute to patient safety and improved outcomes [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe interview results indicated that patients did not receive timely responses from healthcare professionals when experiencing skin toxicity and hoped for more attention from them. This result reflects how, in the clinical environment, healthcare professionals do not pay sufficient attention to skin toxicity issues. Research has shown that the overall level of awareness of cancer immunotherapy among healthcare workers is low [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Healthcare professionals may not have sufficient knowledge about immune therapy\u0026ndash;related adverse reactions, making it difficult for them to provide appropriate health education for patients. A European study showed that nurses had a high level of interest in learning about cancer immunotherapy and an overall positive attitude towards its use; furthermore, the need for nurses to be trained in immunotherapy was higher than that of oncologists and surgeons [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Nurses\u0026rsquo; enthusiasm for learning about immunotherapy should be noted, as enhancing nurses\u0026rsquo; knowledge of immunotherapy and developing effective skin toxicity management practices is imperative. Studies have proposed that immune therapy\u0026ndash;related adverse reactions should be addressed through five stages: assessment, examination, diagnosis, treatment, and monitoring [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Early detection and prompt initiation of treatment may minimize severity and duration of symptoms, thereby improving quality of life and enabling patients to remain in treatment. As healthcare providers with high patient contact, nurses are often asked by patients to check their bodies or review skin pictures to explain the cause of the condition and advise on appropriate management. Nurses play an important role in the management of skin toxicity through early detection, health promotion, and coordination of treatment options with multiple departments. Current guidelines for the management of ICI toxicity are divided into organ categories, and practical guidelines based on clinical experience may be more helpful to healthcare workers in recognizing and managing skin toxicity [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis qualitative study only included results from patients with low-grade cutaneous toxicity, lacking analysis of data from patients with more severe cutaneous toxicity, which may have influenced the results to a certain extent. Additionally, it is possible that some interviews were conducted during either the acute phase or the recovery phase of cutaneous toxicity, which could also have influenced the responses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study highlights the experience of patients with cutaneous toxicity during immunotherapy. The measures taken and emotional reactions demonstrated during the process of experiencing cutaneous toxicity suggest that in future clinical practice, nurses should focus on enhancing patients\u0026rsquo; awareness of immunotherapy and its adverse reactions. They should provide supportive measures to facilitate easier communication between patients and healthcare professionals, ensuring proper management of cutaneous toxicity issues.\u003c/p\u003e "},{"header":"Declarations","content":"\u003ch2\u003eAuthor contribution statement\u003c/h2\u003e\n\u003cp\u003eYang Zhao and Lili Zhang contributed to the study design, research setting contact, and part of the data acquisition. They contributed equally as corresponding authors. Zhihui Yang contributed to the conceptualization, methodology, and drafted the manuscript with input from all authors. Ruiqi Lu is the \u0026lsquo;joint first authorship for her contribution to this manuscript. Other authors have made different contributions to this study, including Investigation, data curation and formal analysis. All authors contributed to the interpretation of the results and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eThe authors thank all the patients who participated in this study for their selfless sharing.\u003c/p\u003e\n\u003ch2\u003eConflict of interest\u003c/h2\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003ch2\u003eFunding sources\u003c/h2\u003e\n\u003cp\u003eThis study was supported by the National Natural Science Foundation of China (grant agreement no.72204106.\u003c/p\u003e\n\u003ch2\u003eData availability Statement\u003c/h2\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL, et al. (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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PubMed: 28436601\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Neoplasms, Immunotherapy, Skin, Qualitative research","lastPublishedDoi":"10.21203/rs.3.rs-3899394/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3899394/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eImmunotherapy has changed the outlook for cancer treatment. A closer look at the accompanying symptoms from the patient\u0026rsquo;s perspective is necessary to improve their tolerance to treatment and is the basis for standardized symptom management.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo describe the symptomatic experience of skin toxicity in cancer patients undergoing immunotherapy.\u003c/p\u003e\u003ch2\u003eDesign:\u003c/h2\u003e \u003cp\u003eQualitative interviews on symptom experiences were conducted from the perspective of cancer patients receiving immunotherapy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA purposive sample of 18 patients with immune-related cutaneous adverse events participated in this semi-structured interview. Transcripts were entered into NVivo 11.0. Qualitative thematic analysis was used to analyze the data for significant statements and phrases, which were organized into themes and subthemes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThree main themes were identified in the data: (I) management of skin toxicity in patients; (II) patients\u0026rsquo; experience of skin toxicity; and (III) problems that skin toxicity poses for patients and the support they would like to receive.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe result enables nurses to better understand and empathize with the patient\u0026rsquo;s experience, to truly practice the essence of patient-centered care, and provide a basis for the development of standardized symptom management programs in the future.\u003c/p\u003e","manuscriptTitle":"Experiences of immune-related skin toxicity: a qualitative study among patients with cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-01 05:57:26","doi":"10.21203/rs.3.rs-3899394/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ec2bca70-80f3-4bfb-914f-7679940c2692","owner":[],"postedDate":"February 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-21T20:14:16+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-01 05:57:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3899394","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3899394","identity":"rs-3899394","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}