Trauma plays an important role in acral melanoma: A retrospective study of 303 patients.

INTRODUCTION: Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. METHODS: A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. RESULTS: Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. CONCLUSION: This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.

Resumption of Intravenous Anti-Cancer Therapy in Breast Cancer: A Real-World Experience During the SARS-CoV-2 Pandemic.

Purpose: The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has delayed medical consultations, especially for patients receiving intravenous anti-cancer therapy. We aim to investigate alterations in immune function among breast cancer patients who experience delayed intravenous therapy due to SARS-CoV-2 infection. Patients and Methods: We performed an observational investigation of breast cancer patients in Nanjing Drum Tower Hospital from December 27, 2022, to January 20, 2023. Patients who recovered from SARS-CoV-2 infection were eligible for enrollment. Peripheral blood samples were taken prior to the restart of intravenous anti-cancer therapy to examine hematologic parameters. Results: A total of 131 patients were included in the final analysis. Cough (74.0%), fever (62.6%), and expectoration (46.6%) were identified as the most presenting symptoms of SARS-CoV-2 infection in breast cancer. The average nucleic acid conversion time and delayed treatment time was 13.4 days and 13.9 days, respectively. The patients >60 years old experienced prolonged nucleic acid conversion time (P = 0.017) and delayed treatment time (P = 0.028) compared to those <= 60 years old. Dysregulated lymphocyte subsets and cytokines were found post-SARS-CoV-2 infection. Treatment-related adverse events of grade 3 or 4 occurred in 7.6% after resuming intravenous anti-cancer therapy. Conclusion: Our findings reveal that the SARS-CoV-2 infection led to imbalanced immune responses and postponed intravenous anti-cancer therapy in breast cancer. The safety report encourages timely resumption of intravenous anti-cancer therapy after adequately weighing the risks and benefits.

Prognostic value of genetic aberrations and tumor immune microenvironment in primary acral melanoma.

BACKGROUND: Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies. METHODS: A total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan-Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM. RESULTS: The median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25-5.29, p = 0.01; HR = 2.77, 95% CI 1.22-6.28, p = 0.02; HR = 3.43, 95% CI 1.51-7.82, p < 0.01, respectively), while patients who received post-surgical treatments had better survival (HR = 0.36, 95% CI 0.17-0.76, p = 0.01). The most frequently altered genes included BRAF (14.5%), KIT (16.9%), NRAS (12%), NF1 (10.8%), APC (7.2%), and ARID2 (6%). Copy number variations (CNV) were commonly found in CCND1 (19.3%), CDK4 (19.3%), MDM2 (14.5%) and FGF19 (12%). CDK4 amplifications was independently associated with shorter OS in AM patients (HR = 3.61, 95% CI 1.38-9.46, p = 0.01). CD8 + T cells (p < 0.001) and M1 macrophages (p = 0.05) were more highly enriched in the invasive margin than in the tumor center. Patients with higher levels of M1 macrophage infiltration in the invasive margin derived markedly longer OS (HR = 0.43, 95% CI 0.20-0.95, p = 0.03). Interestingly, in CDK4-amplified patients, there tended to be a low level of M1 macrophage infiltration in the invasive margin (p = 0.06), which likely explains the poor prognosis in such patients. CONCLUSIONS: Our study provided a comprehensive portrait of the clinicopathological features, genetic aberrations and tumor microenvironment profiles in AM patients and identified candidate prognostic factors, which may facilitate development of additional therapeutic options and better inform clinical management of AM patients. Based on these prognostic factors, further studies should focus on enhancing the infiltration of M1 macrophages, especially in CDK4-amplified AM patients.