Melanoma Research最新文献

The objective of this study was to investigate the clinical characteristics of lipodystrophy induced by immune checkpoint inhibitors (ICIs). Domestic and international databases were searched as of 28 February 2025 and case reports of ICI-associated lipodystrophy were collected. Relevant information including patients' basic information, ICI application, the occurrence of lipodystrophy, etc., were extracted and descriptively analyzed. A total of 11 patients were included in the analysis, including two males and nine females, age from 34 to 76 years, with an average age of 55 years. The primary diseases were mainly lung cancer, melanoma and renal cell carcinoma. The latency period from ICI initiation to lipodystrophy diagnosis ranged from 42 to 540 days. Clinical manifestations included facial fat pad depletion and subcutaneous fat loss in trunk and extremities. Treatment regimens included pembrolizumab ( n  = 3), nivolumab ( n  = 6), cadonilimab ( n  = 1), and nivolumab/ipilimumab combination ( n  = 1). Serum leptin levels were tested in seven patients, and two had serum leptin concentrations <0.5 ng/ml, the others ranged from 0.6 to 61.1 ng/ml. Eight cases had records of glycated hemoglobin testing, of which five cases had glycated hemoglobin ≥6.5%. After being diagnosed with lipodystrophy, seven patients discontinued ICIs while four continued treatment. Four patients received steroid therapy and seven cases had no relevant records. Among the 11 patients, only one patient demonstrated subcutaneous fat improvement, and seven patients' prognosis was not reported. None of the eight patients who discontinued treatment resumed immunotherapy. ICI-associated lipodystrophy presents similar clinical features to conventional lipodystrophy but shows limited reversibility with treatment cessation or steroid intervention, necessitating increased clinical awareness.

Nomograms are commonly used in oncology to assist clinicians in individualized decision-making processes, such as considering sentinel node biopsy (SNB) for melanoma patients. Concurrently, artificial intelligence (AI) is increasingly being utilized in medical predictions. This study aims to compare the predictive accuracy of nomograms and AI platforms for SNB positivity in a real-world cohort of melanoma patients. A retrospective analysis of melanoma patients who underwent SNB from 2020 to 2024 in a single institution was performed. Three open-access nomograms and three public AI platforms were employed to assess SNB positivity based on comprehensive clinical and pathological characteristics. Our cohort comprised 62 melanoma patients who have undergone SNB, of whom 12 (19.4%) were positive. There was no concordance among the three nomograms, nor among AI platforms ( P  < 0.001). Only the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram scored statistically different between positive and negative SNB ( P  = 0.04), and ChatGPT was the only AI platform that was also statistically significant ( P  = 0.02). Only ChatGPT score was statistically significant for SNB positivity after univariate logistic regression (odds ratio: 1.05; 95% confidence interval: 1.004-1.108; P = 0.03). A receiver operating characteristic curve based on ChatGPT predictions generated a model with an area under the curve (AUC) of 0.702. Integrating MSKCC predictions marginally improved the model's predictive performance, enhancing the AUC to 0.715. In conclusion, SNB positivity could be better performed by an AI platform in this cohort of patients. Enhancing AI platforms could provide better populations for nomogram validation, which would lead to better predictive models.

Tinostamustine is a first-in-class alkylating deacetylase inhibitor that facilitates access to cancer cell DNA, resulting in its damage and counteracting DNA repair systems. We hypothesize that the addition of tinostamustine to immune checkpoint inhibitors (ICIs) improves melanoma treatment. This open-label, nonrandomized phase IB study characterized dose-limiting toxicity (DLT) and the recommended dose (RD) of 2-weekly intravenous tinostamustine at escalating doses of 15 and 30 mg/m 2 when administered with 2-weekly nivolumab 3 mg/kg added in cycle 2 in patients with melanoma. We included 17 patients (four at 15 mg/m 2 and 13 at 30 mg/m 2 tinostamustine). A total of 13/17 (77%) patients were ICI-resistant, 7/17 (41%) had unfavorable melanoma subtypes. No DLT was identified. Tinostamustine RD was 30 mg/m 2 every 2 weeks. One patient experienced grade 2 nivolumab-associated immune-related pneumonitis. Tinostamustine-associated grade 3 leukocytopenia was documented in one patient, grade 2 leukocytopenia in five patients, and grade 1 thrombocytopenia in three patients. Treatment discontinuation occurred in one patient for nivolumab-associated immune-related pneumonitis and in another patient for tumor-related hemorrhage. A total of 7/13 (54%) evaluable patients had at least stable disease as best treatment response, including 3/13 (23%) patients with a confirmed partial response. Median progression-free survival was 8.3 weeks [95% confidence interval (CI): 2.4-15.4 weeks), median overall survival was 19.1 weeks (95% CI: 2.4-41 weeks). Two-weekly intravenous tinostamustine at an immune-modulatory dose of 30 mg/m 2 is safe when coadministered with nivolumab 3 mg/kg and resulted in 54% disease stabilization and 23% confirmed partial responses in patients with predominantly ICI-resistant, advanced melanoma.

The National Comprehensive Cancer Network (NCCN) recommended surveillance imaging intervals for uveal melanoma (UM) based on the risk of distant metastasis. The objective of this research is to evaluate if patients, treated at our tertiary cancer center, who had scans consistent with these guidelines, had improved overall survival (OS). This was a single-center, retrospective study of UM patients, who developed metastatic disease. Patients were grouped into risk-of-metastasis cohorts (low, medium, and high-risk) based on the UM NCCN guidelines v1.2023. The frequency of scans was reported within annual intervals for 5 years within the low-risk cohort and for 10 years within the medium-risk cohort, and within 6-month intervals for the first 5 years and then annually in years 6-10 within the high-risk cohort. Conditional landmark analyses were used to evaluate the relationship between OS and consistency with guidelines. Scan frequency was evaluated against socioeconomic status. Of the 740 UM patients identified (1997-2020), 110 experienced metastasis and comprised our analysis population (20 low-risk; 67 medium-risk; and 23 high-risk). The median time to death (95% confidence interval) from diagnosis of metastasis was similar between the low, medium, and high-risk cohorts at 1.2 (1.0, 2.0), 2.0 (1.7, 2.6), and 1.6 (1.3, 2.3) years, respectively. For each cohort, the OS results were similar between those who followed guidelines vs. not at each annual landmark time. Living in disadvantaged areas did not impact imaging frequency (all P > 0.05). Imaging at intervals outlined by the NCCN guidelines v1.2023 did not impact OS for patients who developed metastatic UM.

Goal of this study was to examine the impact of immunotherapy on overall survival (OS) in patients with female genital tract melanoma (GTM). This retrospective cohort study utilized the National Cancer Database to identify individuals with invasive vulvar or vaginal melanoma diagnosed between 2004 and 2019. Kaplan-Meier plots and multivariate Cox regression were used to describe the impact of immunotherapy on OS and to examine predictors of OS among those who received immunotherapy for those with vulvar or vaginal melanoma. Of the 870 patients with vaginal melanoma, 23.6% received immunotherapy. Receiving immunotherapy for treatment of vaginal melanoma was associated with improved OS (median: 21.8 versus 18.9 months; P  = 0.01); this association remained after adjustment for other prognostic factors [hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.62-0.95; P  = 0.01]. The survival advantage was more pronounced among those who did not receive primary surgical resection (median: 18.6 versus 12.2 months; P  = 0.0009). Among 3123 patients with vulvar melanoma, 15.3% received immunotherapy. Receiving immunotherapy for treatment of vulvar melanoma was associated with an improvement in OS (median: 43.6 versus 57.7 months; P  = 0.06; HR, 0.86; 95% CI, 0.74-1.00; P  = 0.04). Survival benefit was more pronounced when restricted to patients with advanced or unknown stage disease (median OS, 31.6 versus 24.2 months; P  = 0.002; adjusted HR, 0.74; 95% CI, 0.61-0.89; P  = 0.002) and among the small subset who did not receive primary surgical resection (median: 19.8 versus 9.6 months; P  = 0.0005). Immunotherapy was associated with improved OS in patients with female GTM, with some subsets particularly benefitting.

In times of limited resources, data on the costs of disease should be one of the primary factors assisting policymakers in attaining the best value for money. This study aimed to analyze the real-world direct costs associated with a 4-year postdiagnosis follow-up of a population-based cohort of patients with cutaneous melanoma stratified by sociodemographic and clinical characteristics. The cost analysis was conducted from the perspective of the health system. Data on visits to outpatient clinics, specialist services, drug prescriptions, hospital or hospice admissions, and treatments at the emergency department were obtained from the regional administrative subject-level databases (see below). The cost of any diagnostic or therapeutic (surgical or otherwise) interventions was based on the reimbursement rates established by the Veneto Regional Authority. This study revealed that direct healthcare costs for patients with melanoma are associated with sociodemographic characteristics, that is, male gender and older age, and anatomopathological factors such as tumor-node-metastasis (TNM) stage, mitotic count, and growth pattern, with the highest costs occurring in vertical growth melanoma. Given the rising incidence of melanoma, the analysis of real-world direct costs for a population-based cohort of patients is essential for informing decision-makers on how to better allocate healthcare resources.

Data regarding circulating tumor DNA (ctDNA) in stage III melanoma are scarce. The main objective was to analyze the usefulness of ctDNA determination in predicting tumor progression in patients with stage III melanoma. A prospective multicenter study was designed based on patients with stage III cutaneous melanoma. We studied BRAF , NRAS , and TERT promoter mutations in primary or metastatic tumors. Blood samples were collected after detecting a positive lymph node by sentinel lymph node biopsy; preoperative in patients with lymph node metastasis; or before any treatment in patients with confirmed unresectable lymph node metastasis or in-transit metastasis; 4 weeks after lymph node surgery (postoperative); and every 3 or 6 months after the baseline sample. From each sample, we isolated cell-free DNA, and previously identified mutations were searched for to identify ctDNA. ctDNA was detected in 21 (21/48, 43.8%) patients. Recurrence at a distant site and recurrence in two or more locations were associated with ctDNA detection at the time of recurrence ( P  < 0.05). Plasma ctDNA detection at any time during follow-up was significantly associated with progression ( P  = 0.011), overall mortality ( P  < 0.001), and melanoma-specific death ( P  < 0.001). We did not find an association between detectable ctDNA before surgery and disease progression; however, patients with detectable postsurgical ctDNA exhibited a lower recurrence-free survival, overall survival, and melanoma-specific survival. Prospective longitudinal blood sampling for the identification of ctDNA provides information regarding recurrence and survival.

Cardiac metastasis from melanoma is a rare but clinically significant condition often underdiagnosed because of its asymptomatic nature. This retrospective case series examines six patients with metastatic melanoma treated at the University Hospital of Bordeaux who were incidentally found to have cardiac metastases during follow-up. The patients were treated with immune checkpoint inhibitors (ICIs) either alone or combined with surgical excision of cardiac lesions. Outcomes were mixed, with three (50%) patients achieving a complete response, one (16.7%) a partial response, and two (33.3%) experiencing disease progression. Cardiac metastasectomy, when combined with ICI, showed promising results in selected patients, highlighting a potential survival benefit and enhanced tumor control with a multimodal approach. This series emphasizes the importance of considering cardiac metastases in differential diagnosis and underscores the role of imaging in early detection. While ICI therapy shows effectiveness, further studies are needed to refine treatment strategies and improve outcomes for patients with cardiac involvement.

C-reactive protein (CRP) kinetics has emerged as a potential biomarker for predicting treatment response and survival in various tumors treated with immune checkpoint inhibitors (ICIs). However, data on CRP kinetics in melanoma are limited. This study evaluates the relationship between CRP kinetic groups and progression-free survival (PFS) and overall survival (OS) in 104 advanced melanoma patients treated with ICIs from 2015 to 2023. Patients were classified into four CRP kinetic groups: CRP flare responders, defined as patients whose CRP at least doubles within 1 month and then falls below baseline by 3 months; CRP responders, whose CRP decreases by ≥30% from baseline within 3 months without doubling; all-normal CRP, whose CRP remains below the upper limit of normal throughout the first 3 months; and CRP nonresponders, who do not meet these criteria. Amongst patients, 64.4% received anti-programmed death-1 monotherapy and 35.6% received the nivolumab-ipilimumab combination. Median PFS was 4.80 months in CRP nonresponders, 10.90 months in CRP responders, 8.83 months in CRP flare responders and 33.57 months in all-normal CRP patients ( P  < 0.001). Similarly, median OS was 11.9 months in CRP nonresponders, 38.1 months in CRP responders, 21.5 months in CRP flare responders and 54.5 months in all-normal CRP patients ( P  < 0.001). Multivariate analysis confirmed CRP kinetic groups as an independent predictor of PFS, OS and objective response. CRP kinetic classification is a simple prognostic tool for advanced melanoma patients treated with ICIs and is associated with improved survival outcomes, underscoring the clinical value of CRP monitoring.