Topical corticosteroid therapy for facial acneiform eruption due to EGFR inhibitors in metastatic colorectal cancer patients: a randomized controlled trial comparing starting with a very strong or a weak topical corticosteroid (FAEISS study, NCCH1512, colorectal part).

BACKGROUND: Although pre-emptive therapy with oral tetracycline, moisturizer, sunscreen, and topical corticosteroid is useful for preventing acneiform eruption (AfE) due to epidermal growth factor receptor (EGFR) inhibitors, no studies have examined the efficacy of topical corticosteroids themselves, or investigated the optimal potency of corticosteroid for treating facial AfE (FAfE). PATIENTS AND METHODS: Screened patients with RAS wild-type colorectal cancer started pre-emptive therapy with oral minocycline and moisturizer on initiation of cetuximab or panitumumab therapy. Patients who developed grade 1 or 2 FAfE were randomly allocated to two groups: a ranking-down (RD) group that started with a very strong corticosteroid and serially ranked down every 2 weeks unless FAfE exacerbated; and a ranking-up (RU) group that started with a weak corticosteroid and serially ranked up at exacerbation. FAfE grade, patient quality of life, and adverse events (AEs) with topical corticosteroid were evaluated every 2 weeks. The primary endpoint was the total number of times grade 2 or higher FAfE was identified in the central review of the 8-week treatment period. RESULTS: No significant differences in total numbers of grade 2 or higher FAfE or in AEs caused by topical corticosteroids were observed between groups during the 8 weeks. Incidence of grade 2 or higher FAfE tended to be lower in the RD group during the first 2 weeks. CONCLUSION: Considering the long-term care of FAfE, the RU regimen appears suitable and should be considered the standard treatment for FAfE due to EGFR inhibitor therapy. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000024113).

Results of the non-small cell lung cancer part of a phase III, open-label, randomized trial evaluating topical corticosteroid therapy for facial acneiform dermatitis induced by EGFR inhibitors: stepwise rank down from potent corticosteroid (FAEISS study, NCCH-1512).

PURPOSE: This FAEISS study was designed to confirm the superior efficacy of reactive topical corticosteroid strategies employing serially ranking-DOWN from very strong steroid levels for the treatment of facial acneiform rash induced by epidermal growth factor receptor (EGFR) inhibitors (EGFRIs), in comparison with strategies employing serially ranking-UP from weak steroid levels. This article reports the primary results of the non-small cell lung cancer (NSCLC) part of the trial. METHODS: Patients with EGFR-mutated advanced NSCLC treated with erlotinib or afatinib were enrolled in the first registration. All patients received preemptive therapy with oral minocycline and heparinoid moisturizer from the initiation of an EGFR inhibitor. Enrolled patients who developed facial acneiform rash within 2 weeks were randomized at second registration to either a ranking-UP (WEAK) group or a ranking-DOWN group. The primary endpoint was incidence of grade ≥ 2 facial acneiform rash over 8 weeks. RESULTS: Fifty-one patients were enrolled at the first registration and received EGFRIs (n = 30 for afatinib, n = 21 for erlotinib). However, 35 patients did not develop facial acneiform rash within 2 weeks; one patient discontinued preemptive treatment. Fifteen patients (29.4%) were enrolled in the second registration; nine were assigned to the WEAK group and six to the DOWN group. There was no significant difference in the incidence of grade ≥ 2 facial acneiform rash between the WEAK group (one patient, twice) and the DOWN group (one patient, twice; p = 0.8417). No patients developed severe facial acneiform rash within 10 weeks. CONCLUSION: In NSCLC patients who received EGFRIs, preemptive therapy of oral minocycline and heparinoid moisturizer reduced facial acneiform rash incidence. TRIAL REGISTRATION: UMIN000024113.

Distress from changes in physical appearance and support through information provision in male cancer patients.

OBJECTIVE: This study aims to reveal the present situation of changes in physical appearance induced by treatment, the effects of these changes on social activities, and support from medical staff in male cancer patients. METHODS: A questionnaire survey was administered to 949 male patients (response rate: 90.1%) visiting the National Cancer Center Hospital in Tokyo over 3 days in January 2015. RESULTS: The final respondents were 823 patients (mean age: 65.3, standard deviation (SD) = 12.32). Fifty-two percent of the sample, and 79.4% of patients aged under 65 were employed. A total of 84.9% experienced changes in physical appearance, and the highest mean scores of psychological were observed for stoma (3.1) and skin eczema (2.9). A total of 66.4% reported no difference in daily life even after their physical appearance changed. However, patients younger than 65 years old who were employed experienced high social difficulties (12.5%). Many wanted to stop going to work and experienced severe distress in their social lives; 74.1% reported it is important to have the same physical appearance at work as before treatment. The majority of patients obtained information from doctors (35.2%) and consulted with their wife or partner (66.2%) regarding their appearance changes, and 5.7% did not have anyone to consult with. CONCLUSION: This study clarified important aspects for supporting male cancer patients: timing, content, target audience and steps of information provision. Appropriate information provision from medical staff prior to treatment can be useful in preparing patients for physical appearance changes and decreasing the severity of symptoms.

The present state and perception of young women with breast cancer towards breast reconstructive surgery.

PURPOSE: This study was conducted to identify factors influencing patients' decisions to undergo breast reconstruction, and to identify the influences of breast reconstruction on patient behavior and psychological well-being. METHODS: Data were collected from January to June 2011, using a questionnaire distributed to women ≤45 years old with breast cancer, at five medical institutes across Japan. RESULTS: Completed questionnaires were collected from 316 women (mean age: 39.46 ± 4.4 years, range: 27-45 years). Overall, 174 patients received breast-conserving surgery, 101 received mastectomy, 31 received subcutaneous mastectomy, 3 patients received none, and 49 were unreported). The data indicated a reconstruction rate of 36.7 % in women who underwent mastectomy. The most prevalent reason for not undergoing breast reconstruction was the fear of cancer relapse. Other factors mentioned were to avoid additional distress on the body from surgery, financial reasons, and a belief that breast reconstruction is unnecessary. The main factor that influenced the decision not to undergo delayed breast reconstruction, specifically, was the expense. Women who had completed breast reconstruction showed higher self-evaluations of physical attractiveness and were more active in comparison to those who did not. However, regardless of having undergone breast reconstruction or not, women who reported higher levels of self-consciousness over the treated areas showed more restrictions on activity and higher chances of a decline in psychological well-being. CONCLUSION: Regardless of deciding to undergo breast reconstruction or not, the results of this study suggested the need for cognitive interventions to avoid patients fixating on self-consciousness over treated areas.

Quantitative assessment of appearance changes and related distress in cancer patients.

OBJECTIVES: This study examined both the frequency of appearance-related symptoms and distress resulting from these symptoms in cancer patients receiving chemotherapy. METHODS: Self-report questionnaires were distributed to 753 outpatients receiving ≧ 4 weeks of treatment at an outpatient chemotherapy center. Valid responses were returned by 638 patients (response rate, 84.7%). Participants were questioned about 57 appearance-related symptoms (AS) and 23 non-appearance-related physical symptoms (non-AS); psychological well-being was assessed using a shortened version of the Derriford Appearance Scale 59. RESULTS: Questionnaire responses were obtained from 264 male and 374 female patients (mean age, 59.5 years; range, 18-85 years). Most respondents (80.3%) were concerned with changes in appearance resulting from treatment. By sex and disease type, women suffered more than men, and treatment for breast cancer created the greatest distress for women. CONCLUSION: Cancer patients are concerned about a variety of AS, and these may result in greater distress than non-AS. AS-related information and care are increasingly being sought in advance of treatment.

Distress and impacts on daily life from appearance changes due to cancer treatment: A survey of 1,034 patients in Japan.

This study aimed to clarify the psychosocial difficulties and impacts that cancer patients face from appearance changes, in order to develop a patient support program. An online survey was administered to patients registered with an online survey company who met the eligibility criteria. The study population was randomly selected from gender and cancer types to create a sample that reflected the proportion of cancer incidence rates in Japan as much as possible. Out of a total of 1034 respondents, 601patients (58.1%) experienced appearance change. Symptoms that were reported to have a high distress level and prevalence rate, and that widely required provision of information were such as alopecia (22.2%), edema (19.8%) and eczema (17.8%). Distress levels and personal assistance requirements were high particularly for patients who experienced stoma placement and mastectomy. More than 40% of patients who experienced appearance change had quit or were absent from work or school, and reported that their social activities were negatively affected by the visually notable changes in their appearance. Concerns about "receiving pity from others" or about "the exposure of cancer" due to their appearance change also led patients to reduce outings (ß = 0.32 and ß = 0.31 respectively, p < 0.001) and social interactions with others (ß = 0.34 and ß = 0.36 respectively, p < 0.001) and increased the discord in human relationships (ß = 0.21 and ß = 0.19 respectively, p < 0.001). Results from this study indicate the areas in which more support is required from healthcare professionals, as well as the need for interventions for patient cognition to avoid maladaptive behaviors in cancer patients who experience appearance changes.

The effectiveness of moisturizer on acute radiation-induced dermatitis in breast cancer patients: a systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to investigate the effectiveness of moisturizers on acute radiation dermatitis (ARD) in breast cancer patients receiving radiotherapy (RT). METHODS: PubMed, the Cochrane Library, CINAHL, and Ichushi-Web were searched for randomized controlled trials (RCTs) from April 2015 to March 2020. Assessments included type of intervention, cohort, outcomes, and quality of evidence. To evaluate the effect of moisturizer on ARD, we restricted analyses to studies comparing with standard skin care or no treatment. Outcomes were ARD severity and skin-related QOL (quality of life). Eligible studies were identified, and risk ratios and mean differences were extracted to compare outcome data. RESULTS: We screened 210 RCTs along with 14 studies included in a previous iteration of this analysis (2016), supplemented by a hand search (n = 9). Finally, we included 6 RCTs that investigated the effectiveness of standard type moisturizers in breast cancer patients receiving RT. Evidence (weak certainty) suggests that moisturizer use might reduce ≥ grade 3 ARD. QOL assessed by Skindex-16 improved with moisturizer use. Pain and pruritus measured by the visual analog scale (VAS) resulted in a smaller and nonsignificant difference in favor of moisturizer use. However, the certainty of the evidence was very weak in QOL. CONCLUSIONS: The proactive use of moisturizer may play a role in reducing ARD and improving skin-related QOL, although the certainty of the evidence was weak to very weak. Future high-quality RCTs should be initiated to strengthen these results.

Development of an educational program for healthcare professionals who provide appearance care for patients with cancer: Feasibility study of an e-learning program.

This study aimed to evaluate the feasibility and utility of an e-learning training program to improve healthcare professionals' knowledge about providing appearance care to patients with cancer. Healthcare professionals who provide appearance support were invited to participate voluntarily and complete a survey before and after the program. Participation request letters were distributed to 133 individuals, including 75 from four facilities invited via professional connections, and agreed to participate in the study and 58 participated in the National Cancer Center's appearance care training and indicated an interest in participating in the study. The 100 participants (75.2%) included 96 females, with an average age of 40.5 years. The participants reported high levels of satisfaction with the program, where more than 90% responded "satisfied" or "somewhat satisfied" and eager to use the content they learned in the program when they returned to their workplaces. However, the participants identified several barriers to applying their newly acquired knowledge including lack of knowledge (about 80%). Participant knowledge scores about appearance support were significantly higher after program participation. The survey results indicated the high feasibility of the e-learning program through improved knowledge about appearance care and high satisfaction with the program. The program needs further improvements for its practical utility.

A Support System for Adolescent and Young Adult Patients with Cancer at a Comprehensive Cancer Center.

Cancer patients in adolescents and young adults (AYA) generation aged 15-39 years have various psychosocial needs during their treatment course such as school enrollment, finding employment, marriage, and fertility. It is difficult for medical professionals to gain experience related to providing medical care and consultation support to these kinds of AYA generation cancer patients. There is a need to provide information and establish both support and medical care systems that are able to meet the diverse needs unique to this generation. This review will explain how to launch an AYA support team (AST). We have worked and established the AST since 2016, which is medical care teams that provide support according to the life stage of each individual patient and build a multidisciplinary AYA generation patient support system. The team-building process consisted of two main projects: building and enlarging multidisciplinary team and establishing screening process of psychosocial needs of AYA generation patients. Multidisciplinary healthcare professionals got involved in the AST with already-existing patient support functions in our center: the patient support center, which is an outpatient department and the palliative care team, which is an inpatient interdepartmental team. The AST systematically finds patients in need of assistance and offers them support as a multidisciplinary team. The AST also established a procedure that systematically gathers information about the needs of patients by using a screening tool. In addition, the AST provides the following specialized services: reproductive medicine, supporting cancer patients with children, employment support, and peer support. The AST has been established and sophisticatedly worked. It can flexibly provide various psychosocial support services. This review will explain how to launch an AST.

Efficacy and safety of topical benzoyl peroxide for prolonged acneiform eruptions induced by cetuximab and panitumumab: A multicenter, phase II trial.

The most common adverse event of epidermal growth factor receptor inhibitors, used to treat colorectal, non-small cell lung, and head and neck cancers, is acneiform eruption, with a profound effect on treatment continuation. Prolonged acneiform eruptions treated with topical corticosteroids, a standard management, may be associated with secondary bacterial infections, thus there is a need for new treatments. We conducted a multicenter, phase II trial to evaluate the efficacy and safety of topical benzoyl peroxide for epidermal growth factor receptor inhibitor-induced prolonged acneiform eruptions. Patients with colorectal, non-small lung cell, and head and neck cancers who received epidermal growth factor receptor inhibitors for >10 weeks and had persistent acneiform eruptions were eligible. Topical benzoyl peroxide was applied to the affected area of the face once daily for 8 weeks; a clinical evaluation was performed every 2 weeks. The primary endpoint was a change in acneiform eruption severity evaluated between disease onset and end of the treatment period. The quality of life of patients was assessed using the Dermatology Life Quality Index. Of the 14 enrolled patients, 11 completed the trial. The protocol-specified grade of acneiform eruptions from baseline to week 8 improved from 2.0 to 1.0 (P < 0.01). The dermatology life quality index score from baseline to week 8 improved from 3.0 to 1.0 point (P < 0.01). No patient experienced severe adverse events. Overall, topical benzoyl peroxide may be effective for treating and managing prolonged acneiform eruptions induced by epidermal growth factor receptor inhibitors.

Non-invasive quantitative measures of qualitative grading effectiveness as the indices of acute radiation dermatitis in breast cancer patients.

BACKGROUND: Recent improvement of machinery evaluation for the skin changes in various therapies enabled us to evaluate fine changes quantitatively. In this study, we performed evaluation of the changes in radiation dermatitis (RD) using quantitative and qualitative methods, and verified the validity of the conventional qualitative assessment for clinical use. METHODS: Forty-three breast cancer patients received conventional fractionated radiotherapy to whole breast after breast-conserving surgery. Erythema, pigmentation and skin dryness were evaluated qualitatively, and biophysical parameters of RD were measured using a Multi-Display Device MDD4 with a Corneometer for capacitance, a Tewameter for transepidermal water loss (TEWL), a Mexameter for erythema index and melanin index. Measurements were performed periodically until 1 year. RESULTS: The quantitative manifestations developed serially from skin erythema followed by dryness and pigmentation. Quantitative measurements detected the effects of irradiation earlier than that of qualitative indices. However, the grades of the domains in RD by qualitative and quantitative assessment showed similar time courses and peak periods. However, no significant correlation was observed between the skin dryness grade and skin barrier function. In contrast to serial increase in pigmentation grades, melanin index showed initial decrease followed by marked increase with significant correlation with pigmentation grades. CONCLUSION: Subjectively and objectively measured results of RD were almost similar course and peak points through the study. Therefore, validity of the conventional qualitative scoring for RD is confirmed by the present quantitative assessments. Instrumental evaluations revealed the presence of modest inflammatory changes before radiotherapy and long-lasting skin dryness, suggesting indication of intervention for RD.

Optical characteristics of human skin with hyperpigmentation caused by fluorinated pyrimidine anticancer agent.

The fluorinated pyrimidine anticancer agent has several side effects that degrade the quality of life of patients, including hyperpigmentation. Hyperpigmentation differs in color from common pigmentation such as a suntan, giving rise to dramatic skin appearance changes. In this study, we measured the optical properties of the skin of patients with hyperpigmentation by using the reflection spatial profile method (RSPM). The absorption coefficient in hyperpigmentation increased ~1.5-2.5 times and pheomelanin significantly increased compared to the normal skin. In addition, the scattering coefficient of skin with hyperpigmentation was about 65.9-76.5% of that of normal skin.

Instrumental evaluation sensitively detects subclinical skin changes by the epidermal growth factor receptor inhibitors and risk factors for severe acneiform eruption.

Epidermal growth factor receptor inhibitors (EGFRI), EGFR tyrosine kinase inhibitors (TKI) and anti-EGFR antibodies commonly develop skin toxicities including acneiform eruption (AfE). However, precise skin changes and risk factors for severe AfE are still unclear. The objective of the current study was elucidation of the useful parameters for early and sensitive detection of the skin changes by EGFRI. Transepidermal water loss (TEWL), skin surface hydration, skin surface lipid levels and erythema/melanin index were serially measured for 2 weeks in 19 EGFR-TKI afatinib/erlotinib-treated patients and for 8 weeks in 20 anti-EGFR antibody cetuximab-treated patients. The TEWL levels of the cheek in the patients who developed AfE of grade 2 and more (AfE ≥ Gr2) were already elevated at 7 days after the initiation of afatinib/erlotinib therapy compared with those before therapy as well as in patients with grade 1 or less (AfE ≤ Gr1). In patients treated with cetuximab, the skin surface hydration on the cheek in AfE ≥ Gr2 patients significantly decreased compared with that of AfE ≤ Gr1 patients at the 2nd and 6th week. Baseline skin surface lipid levels and erythema index on the cheek of patients with AfE ≥ Gr2 were significantly higher than those with AfE ≤ Gr1. The small sample size of the present study, especially for logistic regression analysis, is a limitation. In conclusion, instrumental evaluation declared rapid inflammatory changes of the skin by EGFRI and elucidated oily skin as a risk for severe AfE.

A multicenter survey of temporal changes in chemotherapy-induced hair loss in breast cancer patients.

PURPOSE: Many breast cancer patients suffer from chemotherapy-induced hair loss. Accurate information about temporal changes in chemotherapy-induced hair loss is important for supporting patients scheduled to receive chemotherapy, because it helps them to prepare. However, accurate information, on issues such as the frequency of hair loss after chemotherapy, when regrowth starts, the condition of regrown hair, and the frequency of incomplete hair regrowth, is lacking. This study aimed to clarify the long-term temporal changes in chemotherapy-induced hair loss using patient-reported outcomes for chemotherapy-induced hair loss. METHODS: We conducted a multicenter, cross-sectional questionnaire survey. Disease-free patients who had completed adjuvant chemotherapy consisting of anthracycline and/or taxanes for breast cancer within the prior 5 years were enrolled from 47 hospitals and clinics in Japan. Descriptive statistics were obtained in this study. The study is reported according to the STROBE criteria. RESULTS: The response rate was 81.5% (1511/1853), yielding 1478 questionnaires. Hair loss occurred in 99.9% of patients. The mean time from chemotherapy until hair loss was 18.0 days. Regrowth of scalp hair occurred in 98% of patients. The mean time from the completion of chemotherapy to the beginning of regrowth was 3.3 months. Two years after chemotherapy completion, the scalp-hair recovery rate was <30% in approximately 4% of patients, and this rate showed no improvement 5 years after chemotherapy. Eighty-four percent of the patients initially used wigs, decreasing to 47% by 1 year after chemotherapy and 15.2% after 2 years. The mean period of wig use was 12.5 months. However, a few patients were still using wigs 5 years after completing chemotherapy. CONCLUSIONS: Our survey focused on chemotherapy-induced hair loss in breast cancer patients. We believe these results to be useful for patients scheduled to receive chemotherapy.