Melanoma Research最新文献

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.

Melanoma is among the most common tumors that disseminate to the brain. We analyzed patients with resected early-stage cutaneous melanoma who developed sole brain metastases and brain metastases accompanying other organ spreads and interpreted the clinical characteristics of these patients in this study. A total of 457 patients who developed any organ metastases during or after adjuvant therapy or in follow-up were included in the analysis. A total of 55 (12%) patients had brain metastases (M1d), and 402 patients had other (M1a,b,c) metastases. The majority of brain metastases ( n  = 36, 65.4%) were accompanied by other organ metastases, only 19 patients had sole brain metastases. Brain metastases were mostly in men (76.4 vs. 61.9%, P  = 0.03), and extracerebral dissemination was more commonly associated with acral lentiginous melanoma histopathology (16.7 vs. 4.7%, P  = 0.04). Brain metastasis was found to be associated with shorter survival (median survivals were 6.0 vs. 12.45 months, respectively, P  = 0.0001). However, there was no difference in survival between patients with isolated brain involvements and patients with brain metastases accompanied by spread to other organs (median survivals were 6.0 vs. 5.85 months, respectively, P  = 0.1). In conclusion, brain metastases are a very small portion of relapsed melanoma patients, and the numbers of isolated brain metastases are even smaller, thus the significance of routine brain scans for early detection of brain involvement in the follow-up of patients might be questionable and unnecessary.

This pilot study investigates the relationship between endogenous cortisol and subjective distress and immunotherapy response in patients with advanced melanoma. Patients were asked to donate hair and complete questionnaires. This data was related to immunotherapy response, 3 and 6 months after start. Results from 21 patients were analyzed and showed that there was a significant relationship between depressive symptoms before start of immunotherapy and response 3 and 6 months after start of immunotherapy. Also, a higher baseline level of glucocorticoids was found to be significantly associated with a higher response rate 6 months after start of immunotherapy. The present pilot study warrants further investigation into the relationship between stress and the effectiveness of immunotherapy in patients with advanced melanoma.

Positron emission tomography (PET)/computed tomography (CT) imaging is an established tool in diagnosing and staging for various malignancies, however, during immune checkpoint inhibitor (ICI) therapy not only inflammatory changes may mimic disease progression, but also secondary malignancies should be considered in the setting of unusual clinical and radiographic findings. Here, we present the case of a 64-year-old man with a lymphogenic metastatic malignant melanoma treated with ipilimumab/nivolumab, in whom PET/CT indicated tumor progression of an intra-abdominal mass. Biopsy revealed an unusual reactive T-cell expansion without clonal expansion, pathologically consistent with ICI-induced immune response. As the patient's general condition worsened, we switched to targeted therapy, which had to be discontinued due to increasing fatigue. Follow-up PET/CT at 6 months showed further intra-abdominal progression. Subsequent histopathology of the extirpated mesenteric lymph node conglomerate now revealed diffuse large B-cell lymphoma. Our case highlights the importance of repeated histologic examinations of radiologic pathologies to distinguish secondary malignancies from ICI-induced inflammatory reactions or progressive disease.

This study aimed to evaluate the predictive value of MHC class II (MHC-II) expression by melanoma cells in a large cohort of metastatic cutaneous melanoma patients treated with immune checkpoint inhibitors (ICIs). We conducted a single-center, retrospective study involving stage IV cutaneous melanoma patients who received ICI as first-line therapy. MHC-II expression in melanoma cells was quantified using dual-color anti-SOX10 and anti-MHC-II immunohistochemistry on tumor samples from 95 patients. The primary endpoint was event-free survival (EFS), with secondary endpoints including 1-year EFS, 1-year overall survival (OS), disease control rate (DCR), and the correlation between MHC-II expression and clinico-biological characteristics. The cohort had a median age of 67 years (range, 33-90), with a male-to-female ratio of 50 : 45. Thirty-three percent of patients received the ipilimumab-nivolumab combination. The median follow-up was 16.8 months. Disease progression occurred in 58 patients (61%), with a median time to progression of 4.8 months. Forty-six patients (48.4%) experienced an event within the first year, and 52 patients (54.7%) died during follow-up. MHC-II positivity was observed in ≥10% of melanoma cells in 6.3% of patients. MHC-II expression was significantly associated with 1-year EFS ( P  = 0.037) and DCR ( P  = 0.032), but not with EFS or 1-year OS. Age, phototype, and brain metastases were correlated with MHC-II expression status. Our findings suggest that MHC-II expression by melanoma cells may serve as a favorable predictive biomarker for survival in metastatic cutaneous melanoma patients treated with ICIs.

Immune-mediated acute gastritis (IMAG) is a rare side effect of nivolumab therapy. A 49-year-old patient with metastatic melanoma developed IMAG during nivolumab treatment. In the 5th month of treatment, the patient complained of epigastric pain, nausea, vomiting, loss of appetite, and weight loss. Esophagogastroduodenoscopy and biopsy were performed, and the diagnosis of IMAG was pathologically confirmed. In addition to the discontinuation of nivolumab treatment, proton pump inhibitor and corticosteroid treatment were administered, and the complaints of the patient disappeared after 1 week. Since nivolumab is frequently used in melanoma patients, IMAG should be considered and diagnostic procedures should be performed in patients with symptoms suggestive of acute gastritis during treatment, although it rarely develops.