Alopecia neoplastica: A manifestation of metastatic breast cancer.

We herein report a typical case of alopecia neoplastica secondary to breast cancer. Alopecia neoplastica is a rare form of alopecia resulting from metastasis of a primary tumour to the scalp and is often misdiagnosed as alopecia areata.

Diagnostic accuracy of dermoscopy for 934 basal cell carcinomas: A single-center retrospective study.

Although the efficacy of dermoscopic diagnosis of basal cell carcinoma (BCC) has already been established, most studies have been conducted in Western countries. However, there are racial differences in the clinicopathological characteristics of BCC, highlighting the need for a survey among Asians. Herein, we aimed to investigate the diagnostic accuracy of dermoscopy in 934 Japanese patients with BCC and statistically analyze the clinicopathological factors affecting diagnostic accuracy. We analyzed 5093 skin lesions, including 934 BCCs that were diagnosed consecutively from 1998 to 2018. The sensitivity and specificity of dermoscopic diagnosis for BCC were calculated. The sensitivity and specificity of dermoscopic diagnosis were 92.2% and 96.0%, respectively. There were 73 false-negative cases of BCCs that were clinically diagnosed with other diseases. The most common incorrect clinical diagnosis was seborrheic keratosis (n = 18), followed by melanocytic nevus (n = 15). Multiple logistic regression analysis showed that sensitivity was significantly lower in BCCs located on the trunk and extremities, which showed low pigmentation (less than 10% of the lesion surface) and were diagnosed by a resident dermatologist. Experience of 3-6 months of 12 resident dermatologists revealed increased sensitivity. Dermoscopy is a reliable tool for the accurate diagnosis of BCC in Japanese individuals. Care should be taken when diagnosing BCCs of the trunk and extremities, and the less-pigmented subtype because of lower sensitivity. A certain amount of experience is required to improve the skills for dermoscopy.

Concordance in judgment of clinical borders of basal cell carcinomas in Japanese patients: A preliminary study of JCOG2005 (J-BASE-MARGIN).

Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well-defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato-oncologists may occur. Therefore, we analyzed the dermato-oncologists' concordance in judging the clinical tumor border of basal cell carcinoma. Forty-seven dermato-oncologists (experts: 37; young trainees: 10) participated in this study. The datasets of clinical and dermoscopic photographs of 79 Japanese cases of head and neck basal cell carcinoma were used to determine the concordance in the judgment of clinical tumor border. The probability of the border that was selected more often was used to calculate the rater agreement rate for each dataset. Correct judgment was defined as a more frequently selected border, and the concordance rate of clarity of clinical tumor border for each dermato-oncologist was calculated based on the definition of the correct judgment. A median concordance rate of 85% or higher for all dermato-oncologists was predefined as an acceptable rate for clinical use. Of the 79 datasets, rater agreement rates were 80-100%, 60-79%, and 51-59% for 55, 19, and five datasets, respectively. The median concordance rate for all dermato-oncologists was 86% (interquartile range: 82-89%). There was no significant difference in the concordance rate between the experts and the trainees (median, 87% vs. 85.5%; p = 0.58). The concordance rates of dermato-oncologists for all datasets were relatively high and acceptable for clinical use.

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).

Treatment outcomes of mucosal melanoma of head and neck: Efficacy of immune checkpoint inhibitors for advanced disease.

Background: Head and neck mucosal melanoma (HNMM) is a rare and aggressive subtype of melanoma. HNMM often develops as a recurrent or metastatic disease, and its prognosis is worse than that of cutaneous melanoma. Recent large-scale clinical studies have reported favorable outcomes with immune checkpoint inhibitors (ICIs) for melanoma. However, these clinical trials included only a small number of HNMM cases. This study aimed to estimate treatment outcomes and prognostic predictors of ICIs for advanced HNMM. Methods: Cases of advanced HNMM, defined as unresectable or metastatic HNMM at the initial diagnosis (five patients) or development of recurrent/metastatic HNMM after initial treatment (27 patients), were included in this study. Survival analysis and a search for prognostic factors were performed for these 32 patients. Furthermore, the detailed clinical course of patients who received ICI treatment was investigated. Results: The median overall survival (OS) of 32 patients with advanced HNMM was 25.3 months. The estimated 1-, 3-, and 5-year OS rates were 68.4%, 42.8%, and 34.3%, respectively. Fourteen patients (43.7%) received ICIs, whereas 18 (56.3%) did not. Univariate analysis showed that ICI treatment was the only factor associated with a better 1-year OS. Patients who received ICI treatment had significantly longer OS (median OS: not reached, 1-year OS: 85.7%) than those who did not (median OS: 11.3 months, 1-year OS: 54.5%). The overall response and disease control rates of patients who received ICI treatment were 50% and 64.3%, respectively. Patients who achieved complete response (CR) or partial response (PR) to ICI treatment survived significantly longer (1-year OS: 100%) than those who did not (1-year OS: 71.4%). Among the five patients who discontinued ICI treatment due to severe immune-related adverse events (irAEs), four did not receive salvage treatments but showed durable treatment effects and survived for 9.8-54.2 months at the end of the follow-up period. Conclusions: ICI treatment achieved a favorable OS for advanced HNMM. CR/PR to ICI treatment and discontinuation owing to severe irAEs were favorable predictors of OS.

Observation policy for sentinel node metastasis of melanoma: Comparative study with completion lymph node dissection in Japanese patients.

Based on the results of international multicenter randomized trials, completion lymph node dissection for patients with sentinel lymph node-positive melanoma is no longer routinely recommended. However, clinicians should take into consideration racial and medical resource differences when applying this evidence to clinical practice in Japan. To evaluate the clinical validity of the observation policy of omitting completion lymph node dissection, we retrospectively surveyed patients with sentinel lymph node-positive melanoma between 2002 and 2020 at Niigata Cancer Center Hospital. A total of 59 patients were categorized into the observation group (n = 19) and completion lymph node dissection group (n = 40). Newly developed anticancer agents, including targeted therapy and immunotherapy, were more commonly used in the observation group than in the completion lymph node dissection group as either adjuvant therapy (31.6% vs. 5.0%) or post-recurrence therapy (100% vs. 34.8%). The median overall survival in the observation group (not reached) was significantly longer than that in the completion lymph node dissection group (95.0 months; p = 0.02), which was mainly attributed to the difference in post-recurrence overall survival. There was no significant difference in recurrence-free survival between the two groups (p = 0.63). Although the use of new anticancer agents leads to bias, this study demonstrates that observation without prompt completion lymph node dissection provides a favorable overall survival without increasing the risk of recurrence compared with completion lymph node dissection. The observation policy for patients with sentinel lymph node-positive melanoma patients is considered to be clinically valid in real-world medical practice.

Dermatologist's role in a cancer hospital: An overview of in-hospital consultations.

As cancer treatment advances, the need for dermatologists in the treatment process is increasing. Cancer patients often experience cutaneous manifestations of internal diseases and dermatological adverse events from chemotherapy, radiation, surgery, and stem cell transplants. These diminish patients' health-related quality of life and negatively affect cancer treatment adherence. To identify the dermatologist's role, we analyzed 893 cases of in-hospital dermatology consultations at the Niigata Cancer Center Hospital during 2019. The number of dermatology consultations was the second highest among all hospital departments. Malignant tumors accounted for 91.7% of the underlying diseases, including hematological, gastrointestinal, and lung cancer as the top three primary cancers. The most common consultation category was inflammatory skin disorders (29.2%), followed by chemotherapy-related skin disorders (23.5%), cutaneous infections (11.5%), skin tumors (9.5%), and continued treatment of pre-existing skin disorders (8.8%). The average intervention time was the longest for continued treatment of existing skin disorders (229 ± 60.6 days), followed by malignant wound management (126 ± 60.6 days) and chemotherapy-related skin disorders (122 ± 60.6 days). The median overall survival time of the 27 patients in the malignant wound management group was 5 months (95% confidence interval, 1.8-8.2 months) from the initial dermatology consultation. Our results show an increasing demand for dermatologists in cancer management. However, the number of full-time dermatologists is insufficient in some Japanese cancer hospitals. There is a need to consider increasing the number of adequately trained dermatologists in cancer medical settings.

Trends in the prognosis of metastatic melanoma in the era of targeted therapy and immunotherapy: A single-institution survey in Japan.

Advances in anticancer therapy, including the development of targeted therapy and immunotherapy, have drastically changed treatment options for metastatic melanoma. However, to date, only a few studies have been published that directly compare overall survival (OS) before and after introduction of these new therapeutic options in Japan. We retrospectively surveyed patients with metastatic melanoma treated in our hospital between 1989 and 2019 to investigate the OS benefit of the new therapies. A total of 115 patients with metastatic melanoma (cutaneous origin, 92; mucosal, 14; uveal, two) were included in the study. Kaplan-Meier analysis showed that the patient group receiving targeted therapy/immunotherapy (TT/IT) (n = 47) had a median OS of 19.0 months, which was longer than that in patients receiving conventional chemotherapy (n = 42, 8.0 months) or no treatment (n = 26, 6.0 months) (P < 0.001). In the subgroup analysis performed for the TT/IT group, patients of younger age and with the BRAF mutation had significantly improved OS. As the number of treatment lines increased, the median OS tended to become longer. Our real-world data confirmed an improvement of median OS upon the introduction of the new therapies for metastatic melanoma. However, the long-term OS benefit was limited, possibly because of racial differences in some of the clinical characteristics. To improve the overall melanoma prognosis, the entire treatment strategy, including perioperative therapy needs strengthening.

Risk factors for lymph node metastasis in cutaneous squamous cell carcinoma: a long-term retrospective study of Japanese patients.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin cancers. Prognosis is favorable following surgical resection of early-stage disease, but the management of the metastatic disease is challenging. Several prognostic risk factors have been described in the American Joint Committee on Cancer/the Union for International Cancer Control (UICC) 8th edition staging and the Brigham and Women's Hospital T classification system. However, their clinical validity in Asian populations is unclear because of racial differences in the clinical characteristics of CSCC. This study aimed to identify factors that could predict lymph node metastasis in Asian patients. METHODS: This retrospective single-center study evaluated 540 patients with primary CSCC between 1989 and 2013. Five factors were evaluated for their ability to predict lymph node metastasis: maximum tumor diameter, tumor thickness, depth of invasion, degree of differentiation, and infiltrative growth pattern (INF). RESULTS: Tumor diameter > 2 cm (p < 0.0001), tumor thickness > 6 mm (p < 0.0001), invasion beyond the subcutaneous fat (p < 0.0001), poor differentiation (p = 0.042), and INFc infiltration (p < 0.0001) were associated with lymph node metastasis in the univariate analyses. In the multivariate analysis, lymph node metastasis was independently associated with tumor size > 2 cm [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.4-6.2; p = 0.006], tumor thickness > 6.0 mm (HR 2.9, 95% CI 1.3-6.4; p = 0.007), and invasion beyond the subcutaneous fat (HR 2.3, 95% CI 1.0-5.1; p = 0.045). CONCLUSION: Larger tumor diameter, greater tumor thickness, and deeper invasion included in the UICC T classification system are associated with increased risks of lymph node metastasis from CSCC in Japanese patients.

Final analysis of a phase II study of nivolumab in combination with ipilimumab for unresectable chemotherapy-naive advanced melanoma.

Nivolumab plus ipilimumab combination is currently one of the preferred regimens for advanced melanoma in recently updated clinical practice guidelines. However, the evidence on the efficacy of the combination for acral or mucosal subtypes remains less robust. This is the final analysis of a multicenter, open-label, uncontrolled phase II study that investigated the long-term efficacy and safety in treatment-naive Japanese patients with advanced melanoma, including acral or mucosal subtypes, and subsequent therapy after discontinuation of the investigational agents. Patients received four doses of nivolumab (1 mg/kg i.v.) in combination with ipilimumab (3 mg/kg i.v.) at 3-week intervals, followed by doses of nivolumab (3 mg/kg i.v.) at 2-week intervals. The median follow-up period was 20.8 months (range, 5.2-35.0). The centrally and locally assessed objective response rates were both 43.3% (13/30; 95% confidence interval [CI], 25.5-62.6). Median progression-free survival was not reached (95% CI, 3.02-not reached), and median overall survival was also not reached (95% CI, 19.52-not reached). The 30-month progression-free survival and overall survival rates were 50.3% and 54.2%, respectively. No new safety concerns were detected. After discontinuation of the investigational agents, 83.3% of patients received some form of subsequent therapy including 43.3% of patients who received nivolumab monotherapy and 26.7% of patients who received radiotherapy. Of the four patients who discontinued the investigational agents because of immune-related adverse events, two received subsequent therapy (nivolumab and ipilimumab, respectively) and the other two showed long-term treatment-free survival (659 and 590 days, respectively). Long-term survival with nivolumab plus ipilimumab was observed in Japanese patients with melanoma including acral and mucosal subtypes, which is consistent with the CheckMate 067 study. Many patients continued to receive some form of treatment safely after stopping treatment with nivolumab plus ipilimumab.

Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study.

AIM: The aim of the study was to evaluate the efficacy and safety of nivolumab combined with ipilimumab in treatment-naïve Japanese patients with advanced melanoma. METHODS: In this multicentre, single-arm study, treatment-naïve Japanese patients with unresectable stage III/IV or recurrent melanoma received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four doses, followed by biweekly doses of nivolumab (3 mg/kg). The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included overall survival (OS), progression-free survival (PFS), disease control rate and safety. RESULTS: The subtypes of the thirty patients enrolled were: 12, mucosal; eight, non-acral cutaneous; seven, acral; two, uveal and one, unknown primary melanoma. The ORR was 43.3% (95% confidence interval [CI]: 25.5, 62.6) with central and local assessment. The centrally and locally assessed disease control rate (95% CI) were 73.3% (54.1, 87.7) and 86.7% (69.3, 96.2), respectively. At the median follow-up period of 14.1 months (range 5.2-27.7), median OS and centrally assessed PFS were not reached. OS (95% CI) at 6, 12, 18 and 24 months was 93.3% (75.9, 98.3), 83.3% (64.5, 92.7), 72.9% (50.0, 86.5) and 65.6% (40.4, 82.2), respectively. Treatment-related adverse events (AEs) occurred in all patients. Grade III-IV and serious AEs occurred, mostly during the combination phase, in 23 (76.7%) and 20 (66.7%) patients, respectively. No treatment-related deaths occurred. CONCLUSIONS: This study confirmed the efficacy and safety of nivolumab plus ipilimumab in treatment-naïve Japanese patients with advanced melanoma including rare subtypes. Incidence rates for grade III-IV AEs were high but manageable with appropriate medical attention and treatment. TRIAL REGISTRATION: JapicCTI-152869.

A case of pure red cell aplasia during nivolumab therapy for cardiac metastatic melanoma.

Nivolumab is an antibody against programmed cell death 1 and functions as an immune checkpoint inhibitor for various malignancies, including unresectable melanomas. Nivolumab causes several immune-related adverse events, which typically include skin rash, pneumonitis, thyroid dysfunction, hepatitis, and colitis; in rare cases, anemia may be present. There are several reports of autoimmune hemolytic anemia that has developed in response to nivolumab; however, there are few reports of pure red cell aplasia (PRCA). We describe a patient who developed PRCA during nivolumab administration. A 70-year-old Japanese woman received nivolumab for cardiac metastasis from malignant melanoma from an unknown site. Twenty-one months after nivolumab administration (31 courses), treatment was discontinued because she developed severe anemia. Blood test results indicated normocytic, normochromic anemia, and reticulocytopenia, but all other components were normal. Bone marrow aspiration showed increased megakaryocytes and decreased erythroblasts; these findings were consistent with PRCA. Anemia improved without recurrence after treatment with corticosteroids and blood transfusions. The steroid dosage was reduced gradually, and to date, the patient has not experienced recurrence of anemia. The tumor decreased in size and the patient has shown a continued response to treatment with decrease in disease for 3 years. Although it is unclear how nivolumab causes PRCA, hematological toxicities have been reported in patients treated with immunotherapy drugs. PRCA might be an unrecognized immune-mediated adverse event that did not manifest during the clinical trial phase.

Investigating the use of tie-over dressing after skin grafting.

Tie-over bolster dressing after skin grafting can prolong operative time, and cause hematoma and seroma formation because of uneven pressure application. To describe the possibility of discontinuing the use of tie-over dressing, we carried out a retrospective comparative study of patients who underwent skin grafting at an institution between January 2009 and December 2014. We investigated and compared the take rate, healing period, wound infection rate and hematoma formation rate for the tie-over dressing group and the non-tie-over dressing group. Among 266 patients, 148 and 118 patients were included in the tie-over dressing group and non-tie-over dressing group, respectively. There were no significant differences between the take rate, healing period, wound infection rate and hematoma formation rate for the two groups. Multivariate analysis showed that the complete graft take rate was not significantly influenced by tie-over dressing, age, sex, graft site, graft procedure and skin graft diameter. Although the use of tie-over dressing might remain necessary on sites with a free margin, including the eyelids, lips or nostrils, because of the difficulty in using tape fixation, the present study showed that alternative dressing with polyurethane foam is also useful in most cases of skin grafting.

Long-term prognosis after surgical excision of basal cell carcinoma: a single institutional study in Japan.

Conventional surgical excision (SE) is commonly used to treat patients with basal cell carcinoma (BCC). There have been few studies, however, evaluating the long-term prognosis of Japanese patients receiving SE for treatment of BCC. The purpose of this retrospective study is to determine the effectiveness of SE in accomplishing the long-term cure of patients with BCC. We enrolled 290 patients with primary BCC who underwent SE during 1998-2006. The prognosis of treated patients was subsequently investigated using data obtained through our hospital cancer registration section. In total, 205 patients (70.7%) were treated for BCC lesions located on the face. The mean tumor diameter of excised lesions was 12.8 mm. A majority of patients in the study (256 patients, 88.3%) had pigmented BCC. The mean surgical margin at SE was 3.8 mm. Two patients developed local recurrence during the postoperative course of 290 patients (mean duration, 80 months). One patient developed recurrent disease 21 months after surgery, and the other developed recurrence at 66 months after surgery. The 5- and 10-year cumulative recurrence rates were 0.4% and 0.8%, respectively. In conclusion, this study demonstrated that long-term high cure rates of BCC in Japanese patients may be achieved through conventional SE. A better prognosis was obtained in this study compared with similar studies reported previously in Caucasians. This may be related to the predominance of pigmented versus non-pigmented lesions in the Japanese population.