Melanoma Research最新文献

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.

Pregnancy-associated melanoma is melanoma that can develop up to 1 year postpregnancy. There is no solid evidence on how pregnancy can affect melanoma survival, recurrence, or mortality. This systematic review and meta-analysis aims to analyze the overall survival (OS), recurrence, and mortality rate in pregnant women diagnosed with melanoma. A comprehensive search was performed on Medline, Embase, and Web of Science to identify studies comparing melanoma in pregnant versus nonpregnant women. Hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model. Heterogeneity was evaluated using the I2 statistic, and significance was defined as P values less than 0.05. Statistical analyses were conducted using RStudio 4.4.1. Our meta-analysis included 15 studies, consisting of 29 095 patients; 2917 (10%) were pregnant women. In the OS outcome, statistically significant differences were observed, favoring pregnant women in comparison to nonpregnant women; both groups were diagnosed with melanoma (HR: 0.81, 95% CI: 0.69-0.95, P  = 0.012, I2 = 85.4%). The OS at 5 years did not show statistically significant differences (OR: 1.08, 95% CI: 0.50-2.35, P  = 0.83, I2 = 57.9%). Similarly, the outcomes of melanoma recurrence (RR: 1.19, 95% CI: 0.95-1.48, P  = 0.12, I2 = 0%) and mortality (RR: 1.60, 95% CI: 0.82-3.13, P  = 0.16, I2 = 73.5%) also showed no statistically significant differences between groups. According to this systematic review and meta-analysis, pregnant women diagnosed with melanoma have a higher OS rate than nonpregnant women.

Sentinel lymph node biopsy (SLNB) is a critical procedure in the management of melanoma, offering prognostic information and guiding adjuvant therapy. Glycoprotein nonmetastatic melanoma protein B (GPNMB), a melanogenesis marker, has been implicated in melanoma progression. This study investigates the expression patterns of GPNMB in SLN metastases and their association with oncological outcomes. We conducted a retrospective analysis of 27 melanoma patients with positive SLNB at Tel Aviv Sourasky Medical Center between 2010 and 2020. Immunohistochemistry was used to assess GPNMB expression in SLN metastases, categorizing patients into two groups based on GPNMB expression patterns: homogeneous (GPNMBho) and margin high (GPNMBmh). Peri-tumoral CD8+ T cell infiltration was also evaluated. Clinical outcomes, including melanoma-specific survival (MSS) and disease-free survival (DFS), were analyzed. GPNMB expression in SLN metastases displayed two distinct patterns: uniform (GPNMBho) and high at the tumor margins (GPNMBmh). Patients in the GPNMBmh group had significantly more peri-tumoral CD8+ T cells and exhibited improved MSS (127.6, 95% CI: 111.7-143.5 vs 79.5, 95% CI: 48.2-110.9 months, P  = 0.018) and DFS (107.5, 95% CI: 79-135.8 vs 38, 95% CI: 15.2-60.8 months, P  = 0.04) compared to the GPNMBho group. Multivariate analysis confirmed that GPNMB expression pattern and lymph node metastasis size were independent predictors of both MSS and DFS. GPNMB expression patterns in SLN metastases are strongly associated with long-term oncological outcomes in melanoma patients. The GPNMBmh pattern, characterized by higher margin expression and increased CD8+ infiltration, may serve as a prognostic biomarker for recurrence if validated in larger cohorts.

Pyrexia is the most common adverse event in patients treated with dabrafenib plus trametinib. However, the pathogenesis of pyrexia and factors to identify patients at higher risk of developing pyrexia remain unknown. The ELDERLYMEL study was a multicenter, noninterventional, retrospective, real-world study comparing the effectiveness and safety of dabrafenib plus trametinib between elderly (≥75 years, n  = 29) and younger (<75 years, n  = 130) advanced melanoma BRAF V600-mutated patients in Spain. Surprisingly, pyrexia was significantly less frequent in elderly patients (13.8%) than in younger (42.3%). The post hoc analysis presented here aimed to investigate the relationship between age and pyrexia, applying logistic regression models. Patients <75 years had 4.59 more possibilities to develop pyrexia than elderly patients. The possibility of developing pyrexia increased by 1.03 as age decreased by 1 year. Receiver operating characteristics curves identified 61.5 years as the optimal cutoff value to predict the onset of pyrexia. The age-adjusted regression model revealed that patients <61.5 years had 2.53 more possibilities to develop pyrexia than those ≥61.5. This study demonstrates, for the first time, that age significantly influences the development of pyrexia in patients with BRAF V600-mutated advanced melanoma receiving dabrafenib plus trametinib. Age should be considered in the management and follow-up of these patients but should not limit treatment decisions. These findings provide important insights for clinical practice and contribute to a better understanding of pyrexia in elderly patients. The constructed nomogram based on age could serve as a useful tool for estimating the risk of pyrexia in patients receiving this treatment.

Melanoma metastasis poses a significant challenge due to its aggressive nature and increasing incidence. Confirming the clonal relationship between the primary melanoma and its metastasis is essential to developing reliable prediction models. Here, we compared the genetic profile of primary melanoma and matched metastasis to assess their genetic clonal relationship. Using a targeted sequencing panel encompassing 330 amplicons, we targeted hotspot regions in 41 cancer genes and 154 single nucleotide polymorphisms. The clonal relation between primary and matched metastasis tumors was evaluated by comparing the mutational status and the copy number variations profile in 15 patients with primarily thin melanomas and distant metastases, or with a long latency between the primary melanoma and distant metastasis. Our findings revealed that only about 50% of the analyzed matched primaries and metastases were clonally or likely clonally related, while the remaining sets were either not clonally related or difficult to determine with certainty the clonal relatedness. The findings of our study illustrate the intricate clonal relationships between primary melanoma and metastasis and raise doubts if the metastatic potential is overestimated in the primary tumors. Further investigation with larger cohorts is needed to better understand this complexity of melanoma metastasis and clonality phenomenon, which should be carefully considered when using primary tumor molecular profiles for prognostic model building or therapeutic guidance in metastatic cases.