Melanoma Research最新文献

The use of immune checkpoint inhibitors (ICI) in the elderly population remains challenging because of age-related factors and lack of evidence due to underrepresentation in clinical trials. This retrospective study aimed to assess the efficacy and safety of ICI in elderly melanoma patients compared with younger individuals, to describe their toxicity profile, and to analyze the influence of health status. We included 93 melanoma patients treated with ICI from January 2016 to July 2024 at a single institution. Patients were grouped by age: less than 65, 65-74, and greater than or equal to 75 years. Baseline characteristics, treatment data, progression-free survival (PFS), overall survival (OS), adverse events and geriatric assessments (ECOG Performance Status, Charlson Comorbidity Index and G8 Frailty Scale) were analyzed. Statistical analyses included Kaplan-Meier and regression models. Survival outcomes were comparable across age groups. In advanced disease, patients over 65 showed improved mean PFS [40.2 vs. 17.1 months, P = 0.036; hazard ratio: 0.49, 95% confidence interval (CI): 0.25-0.95]. OS did not differ significantly. Older patients had lower overall toxicity rates (46-50 vs. 74% in <65 years, P = 0.008; odds ratio: 0.31, 95% CI: 0.13-0.75), with fewer grade 3 adverse events. No association was found between comorbidity indices or frailty status and increased toxicity. Adverse events were predominantly mild-to-moderate, mainly skin-related and constitutional; grade 3 adverse events and gastrointestinal symptoms were more frequent in less than 65 years. In conclusion, immunotherapy is effective and well-tolerated in elderly melanoma patients, neither advanced age nor frailty status alone should restrict its use.

To develop a noninvasive diagnostic model integrating deep learning and radiomics for improving the accuracy and clinical utility of early melanoma diagnosis. A total of 350 patients with cutaneous pigmented lesions admitted to our hospital between January 2022 and December 2024 were retrospectively enrolled and randomly divided into a training set ( n  = 245) and a validation set ( n  = 105) in a 7:3 ratio. Complete information were obtained for all patients. Univariate analysis was used to screen factors associated with malignant melanoma. Variables were refined using the least absolute shrinkage and selection operator regression, and independent predictors were identified via multivariate Logistic regression. Random forest (RF), support vector machine (SVM), and K-nearest neighbors (KNN) models were constructed using Python 3.8.5 and the sklearn library. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results from univariate analysis and multivariate logistic analysis showed that lesion diameter, entropy (first-order statistic), long run emphasis, large area emphasis, wavelet contrast, wavelet energy, and the ResNet50-layer49 output were independent risk factors for malignant melanoma (all P  < 0.05). The AUC of the RF model (0.794) was significantly higher than that of the KNN algorithm model (0.755) and the SVM model (0.768), making it the optimal model. The RF model constructed based on deep learning-based radiomics features can be effectively applied to the noninvasive diagnosis of melanoma in patients with cutaneous pigmented lesions. Among these features, entropy (first-order statistic), long-run emphasis, and wavelet contrast are the key predictive indicators.

Mucosal melanoma (MM) is an aggressive and rare subtype of melanoma, and it is associated with poor prognosis. Surgical resection remains the mainstay of the treatment for localized disease, and different from cutaneous melanoma, the impact of adjuvant therapy has not been clearly established. We retrospectively analyzed patients with surgically resected MM from the MD Anderson Cancer Center melanoma database from January 2000 to December 2019. The univariate log-rank test and multivariate Cox regression model were used to analyze the impact of adjuvant therapy on overall survival (OS) and relapse-free survival. A total of 246 patients with localized or locally advanced MM who underwent surgical resection were included. The median OS for all patients was 4.8 years [95% confidence interval (CI), 3.6-6], with median OS for the 125 patients who received adjuvant systemic therapy was 5.7 years (95% CI, 4.0-10.2) and 4.0 years (95% CI, 2.8-6.6) for the 121 patients who had only surgery or surgery plus radiation in the subanalysis, chemotherapy was associated with a longer OS (7.3 years; 95% CI, 4.4-NA) compared to immunotherapy (5.5 years; 95% CI, 2.8-NA). Cox regression analysis demonstrated lymph node involvement, Breslow thickness, and use of adjuvant systemic therapy were considered independent factors for OS. Adjuvant systemic therapy was associated with a significant survival benefit in patients with resected MM (HR 0.53; 95% CI, 0.34-0.82; P  = 0.004). However, due to the retrospective nature of the study, prospective clinical trials are warranted to determine the optimal adjuvant treatment strategy for this patient population.

This case report and literature review detail and contextualise the finding of a positive sentinel node in the contralateral axilla of a 69-year-old male with cutaneous malignant melanoma of the left chest wall. Excision biopsy confirmed nodular melanoma (Breslow thickness 6.6 mm; mitotic index 11; no ulceration or microsatellites; completely excised; pT4a). Preoperative lymphoscintigraphy identified the sentinel node in the right axilla. The patient underwent wide local excision with 2-cm margins and a sentinel lymph node biopsy, which showed no spread of disease. This was followed by six cycles of adjuvant pembrolizumab with surveillance scans remaining clear. Literature review identified 22 cases of anterior chest wall melanoma ( n  = 4) or breast carcinoma ( n  = 18) with contralateral drainage (12 case reports, two case series, and eight retrospective studies). Only one previous chest wall melanoma case with contralateral drainage was identified, but details were not reported. Thus, we present the first documented case of anterior chest wall melanoma with a contralateral sentinel node, and emphasise the importance of thorough evaluation of suspicious lesions for unexpected drainage patterns.

The treatment of metastatic melanoma has been revolutionized with the introduction of immune checkpoint inhibitors, though approximately 50% of patients will progress at 12 months even with the most robust immunotherapy combinations. As these drugs are now first-line treatment for advanced melanoma, it is imperative to define the role and benefits of multimodal therapy adjunct to systemic therapy. This case describes a patient with v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutant stage IV melanoma who has been treated for over 9 years with a combination of systemic and local therapeutics: anti-Cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-programmed cell death protein 1 receptor (PD1), and targeted therapies, stereotactic radiosurgery, and multiple metastasectomies. Through multidisciplinary care with the help of genomic analysis, this patent's survival has been extended far past conventional estimates. Molecular profiling revealed an acquired NRAS mutation, which helped explain clinical findings and allowed for a more tailored therapeutic regimen. This report demonstrates that effective surgical resection of nonresponding or progressing lesions can lead to long-term survival even in patients with severe disease burden. Continuous clinical and molecular monitoring can also help shape patients' treatment courses. The effectiveness of multimodal treatment, incorporating local therapies with molecular profiling in conjunction with systemic therapies, should be considered by interdisciplinary care teams to strive for durable survival in patients with historically grim prognoses.

Artificial intelligence (AI) powered mobile health (mHealth) apps are emerging as vital self-triage tools for skin cancer detection. By utilizing smartphone cameras, these apps analyze skin lesions to assess the risk and provide tailored care recommendations, ranging from self-care guidance to directing users to appropriate healthcare providers. While this positively impacts Sustainable Development Goals 3, the rapid proliferation of these apps introduces significant challenges. A persistent digital divide, stratified by gender, geography, income, and education, limits widespread adoption. It is further exacerbated by varying levels of digital literacy and patient anxieties. The unregulated nature of commercial app stores poses diagnostic risks. At the same time, limited training data for AI models exposes individuals with underrepresented skin types to significant diagnostic errors. Increased self-diagnosis leads to increased downstream care pressures, overwhelming dermatology and pathology services in LMICs. This review highlights the increasing incidence of skin cancer and discusses the risk-benefit profile of mHealth apps in diagnosis. It covers the multifaceted challenges confronting LMICs, including the evolving and fragmented regulatory landscape, while comparing them with those of high-income countries. Finally, we developed a causal loop diagram (CLD) to facilitate informed multistakeholder action for improving public health outcomes through AI-based mHealth apps. The CLD establishes the positive and negative associations of key variables across four pillars: data acquisition and quality, AI model development and validation, user experience and accessibility, and public health impact. We advocate for a multidisciplinary convergence among dermatological experts, AI scientists, app developers, and regulators, fostering international collaboration, knowledge sharing, best practices, and targeted capacity building to ensure equitable and accountable mHealth deployment in LMICs.

Invasive cases of melanoma have increased by 44% annually in the past decade. B-Raf serine-threonine kinase (BRAF)/Mitogen-activated protein kinase kinase (MEK) inhibitors have become the standard of care for stage III/IV BRAF mutant melanoma. Due to limited adverse event (AE) data based on clinical trials, we aimed to describe and compare the AE and outcomes associated with melanoma therapies. A retrospective disproportionality analysis was conducted to assess and compare the trends of AEs associated with BRAF/MEK inhibitors and combinations. The primary data were extracted from the Food and Drug Administration (FDA) Adverse Event Reporting System database from 2012 to 2021. Study drugs included BRAF/MEK inhibitors (dabrafenib, trametinib, vemurafenib, cobimetinib, encorafenib, and binimetinib). A reporting odds ratio (ROR) was calculated for the most common AEs and outcomes reported. We found 195 640 unique AE reports associated with BRAF and MEK inhibitor usage, representing 52 772 patients. The leading AEs associated with BRAFi and MEKi use were as follows: pyrexia, fatigue, nausea, diarrhea, rash, vomiting, and arthralgia. Encorafenib and binimetinib had significant odds for nausea [ROR, 1.91 (1.73-2.11) and ROR, 1.91 (1.73-2.11), respectively]. The incidence of fatigue was highest in the encorafenib [ROR, 1.71 (1.54-1.90)], binimetinib [ROR, 1.74 (1.57-1.94)], and vemurafenib [ROR, 1.27 (1.14-1.27)] groups. Cobimetinib had significantly increased odds for developing a disability [ROR, 4.95 (4.28-5.74)], having a hospitalization [ROR, 2.08 (1.99-2.17)], and experiencing a life-threatening event [ROR, 1.78 (1.55-2.03)]. AE reports associated with melanoma therapies are sizable and significant. Healthcare professionals should be aware of the AE profiles attributable to the melanoma treatment and management.

Reexcisions for melanoma do rarely present residual melanoma. To analyze the number of positive margins in reexcisions of in situ and <1 mm melanomas. To see whether the immunohistochemical (IHC) panel (Preferentially expressed antigen of melanoma (PRAME), Sry-related HMg-Box gene 10 (SOX 10), Human melanoma black 45 (HMB45), and Melan A) detected additional cases of melanoma. Three pilot cohorts (retrospective, prospective, and direct safety margins) were analyzed on the persistence of melanoma in reexcisions. Among the 97 cases of the retrospective cohort (27 in situ and 69 invasive melanomas), one residual in situ melanoma was detected in the reexcisions. In the second cohort, among 81 cases (18 in situ and 63 invasive melanomas), two cases (2.5%) presented in situ melanoma. In the group where direct margins were taken ( n  = 21) 2 (9.5%) in situ melanoma were evidenced in the margins. The IHC panel was needed to confirm three additional in situ melanomas in cohort 2. In a total of 178 cases (97 + 81) of reexcision, three and five cases (1.7 and 3.4%) of in situ melanoma were evidenced after H/E and IHC, respectively. These pilot data could question the usefulness of reexcision in <1 mm melanomas, particularly as only cases of in situ melanoma were detected. Larges prospective series would be required to answer this issue.

Uveal melanoma is a rare malignancy with a strong propensity for late metastases, most commonly affecting the liver. Pulmonary metastases are less frequent and can manifest years or even decades after the primary diagnosis. This study presents three cases of pulmonary metastases secondary to uveal melanoma, highlighting clinical presentations, treatment strategies, and outcomes following surgical intervention. A retrospective analysis of 132 patients diagnosed with uveal melanoma between 2009 and 2022 at one institution was conducted. Clinical and pathological data were reviewed to assess primary tumor characteristics, metastatic patterns, treatment approaches, and patient outcomes. Three patients were identified with pulmonary metastases, diagnosed at least a decade after primary tumor treatment. The metastatic presentation varied, with one patient exhibiting bilateral multiple nodules, while the other two had solitary pulmonary lesions. All patients underwent video-assisted thoracoscopic surgery wedge resection, confirming metastatic melanoma. Two patients remained disease-free following resection, while one developed systemic progression with small bowel metastases, ultimately leading to fatal complications. Surgical resection of isolated pulmonary metastases from uveal melanoma may offer clinical benefit in highly selected patients. While not a standard treatment modality, pulmonary metastasectomy may be appropriate in selected patients and can be considered within the context of a multidisciplinary evaluation.

As a highly aggressive skin cancer, melanoma presents substantial clinical challenges stemming from its metastatic potential and therapy resistance, primarily driven by epithelial-mesenchymal transition (EMT). This review examines EMT's central role in melanoma progression. Molecular mechanisms are detailed, encompassing transcription factors (ZEB1, Snail, Twist), signaling pathways (transforming growth factor beta/Smad, Wnt/β-catenin, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase/extracellular signal-regulated kinase), plus epigenetic and noncoding RNA regulators. Through extracellular matrix remodeling and phenotypic plasticity, EMT potentiates melanoma cell invasion. This facilitation enables key metastatic cascade steps: intravasation and distant colonization. EMT further drives resistance to both targeted therapies (BRAF/MEK inhibitors) and immunotherapies. Mechanisms include T-cell exclusion, PD-L1 upregulation, and immunosuppressive tumor microenvironment remodeling. Tumor progression is amplified via EMT interactions with stromal components, including cancer-associated fibroblasts and immune cells. Prognostically valuable biomarkers are emerging, particularly EMT gene signatures detectable in circulating tumor cells and tissue samples. Preclinical studies suggest therapeutic potential for strategies targeting EMT transcription factors, signaling pathways, and combination approaches. Despite progress, limitations endure: EMT heterogeneity and inadequate preclinical models. Future work will leverage single-cell analysis and spatial transcriptomics to decipher EMT dynamics. Such advances could enable personalized melanoma treatments. EMTs' multifaceted role is underscored herein, along with the urgent requirement for innovative therapeutics to enhance patient outcomes.