Melanoma Research最新文献

{"title":"Programmed death ligand-1 PET imaging in patients with melanoma: a pilot study.","authors":"Neeta Pandit-Taskar, Audrey Mauguen, Denise Frosina, Achim Jungbluth, Klaus J Busam, Serge Lyashchenko, Jazmin Schwartz, Parisa Momtaz, Allison Betof Warner, James W Smithy, Alexander N Shoushtari, Margaret K Callahan, Paul B Chapman, Michael A Postow","doi":"10.1097/CMR.0000000000001050","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001050","url":null,"abstract":"<p><p>Programmed death ligand-1 (PD-L1) is an inducible protein heterogeneously expressed in melanoma. Assessment of PD-L1 expression is challenging and standard immunohistochemistry (IHC) requires biopsies and cannot capture heterogeneity of expression. Noninvasive imaging methods provide evaluation of expression across lesions in the body. We conducted a prospective pilot trial with PD-L1 PET imaging with [18F]-BMS-986229 as a noninvasive approach to assess PD-L1 expression across lesions, in 10 patients with advanced melanoma, longitudinally during treatment with nivolumab and ipilimumab. PET imaging was performed at baseline and at 6 weeks after-initiation of treatment. We examined the relationship of PD-L1 PET uptake to radiographic clinical response. [18F]-BMS-986229 uptake was variably seen across lesions in patients at baseline. All patients showed positive uptake in lesions at baseline PET with a median SUVmax of 3.6 (range: 1.7-8.6). PD-L1 PET SUVmax decreased in all but two lesions 6 weeks after treatment initiation. Four of five patients had a mean (SUVmax) greater than or equal to 3.00 in Response Evaluation Criteria in Solid Tumors (RECIST) evaluable lesions at baseline, and all had a RECIST response while all progressors (n = 3) had baseline PD-L1 mean SUVmax less than or equal to 2.60. A higher lesional baseline SUVmax was associated with greater individual lesion reduction during treatment. The PD-L1 uptake in lesions showed a low correlation with baseline PD-L1 by IHC. In this small pilot study, PD-L1 PET imaging using [18F]-BMS-986229 showed feasibility in noninvasively assessing lesion uptake and PD-L1 heterogeneity in patients receiving combination immunotherapy. Future exploration of this tracer in larger patient cohorts is necessary to delineate its use in managing immunotherapy treatments.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updated meta-analysis on the risk of melanoma associated with phosphodiesterase type 5 inhibitors.","authors":"Michele Kreuz, Francisco Cezar A Moraes, Artur O M Lôbo, Renata P H Skov, Thais P Pincelli","doi":"10.1097/CMR.0000000000001049","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001049","url":null,"abstract":"<p><p>Phosphodiesterase type 5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction, with modest adverse effects. Since 2011, concerns have arisen about increased melanoma risk in PDE5 inhibitor users. PDE5 inhibitors affect the rat sarcoma virus oncogene-rapidly accelerated fibrosarcoma-mitogen-activated protein kinase-extracellular signal-regulated kinase signaling cascade, which is involved in melanoma formation. This systematic review and meta-analysis investigates melanoma risk in PDE5 inhibitor users. PubMed, Cochrane, and Embase were searched to examine the relationship between PDE5 inhibitors and melanoma. A random-effects model estimated pooled odds ratios (ORs) and hazard ratios (HRs), with the I ² statistic assessing heterogeneity. RStudio v4.4.2 was used for the meta-analysis, and a P value less than 0.05 was deemed significant. Eight studies including 7 620 765 patients were analyzed, with 2 123 165 (27.86%) comprising the PDE5 inhibitor-exposed group. The meta-analysis found a relationship between PDE5 inhibitor use and increased melanoma risk [OR: 1.60, 95% confidence interval (CI): 1.13-2.27, P = 0.009, I ² = 98%] and [HR: 1.10, 95% CI: 1.03-1.17, P = 0.005, I ² = 43%]. When each PDE5 inhibitor was examined separately, increased melanoma incidence was observed, though not statistically significant. The OR for sildenafil was 1.85 (95% CI: 0.97-3.51, P = 0.059, I ² = 99%), tadalafil 1.54 (95% CI: 0.79-3.00, P = 0.203, I ² = 96%), and vardenafil 1.16 (95% CI: 0.82-1.64, P = 0.391, I ² = 89%). This study suggests PDE5 inhibitor users have a higher chance of developing potentially fatal melanoma. Patients with a history of skin cancer, a family history of melanoma, or other risk factors should avoid these medications.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postimmunotherapy antiglial fibrillary acidic protein encephalomyelitis after adjuvant pembrolizumab for melanoma.","authors":"Inès Berkaoui, Linda Zourdani, Raphaël Janela-Lapert","doi":"10.1097/CMR.0000000000001048","DOIUrl":"10.1097/CMR.0000000000001048","url":null,"abstract":"<p><p>Pembrolizumab is an immune checkpoint inhibitor targeting programmed cell death protein 1 , used for stage IIB/IIC melanoma. While effective, pembrolizumab can lead to immune-mediated toxicities in various systems; however, nervous system effects are less well-documented. We report the case of a 34-year-old man who developed delayed immune-mediated encephalomyelitis with antiglial fibrillary acidic protein (GFAP) antibodies after completing nine cycles of adjuvant pembrolizumab for stage IIC melanoma. Four months posttreatment, he presented with neurological symptoms, including ataxic gait, sensory deficits in the lower limbs, and urinary retention. Imaging revealed extensive myelitis and encephalitis in the spinal cord and posterior fossa. The etiological evaluation was negative except for the presence of anti-GFAP antibodies in the cerebrospinal fluid. Treatment with high-dose corticosteroids led to significant improvement. This case represents the first reported instance of postimmunotherapy encephalomyelitis with anti-GFAP antibodies following pembrolizumab treatment. Although rare, this is a serious adverse event requiring careful monitoring and early multidisciplinary management.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of expression and prognostic implication of glycoprotein nonmetastatic protein B (GPNMB) expression in sentinel lymph nodes of melanoma patients.","authors":"Ariel Beitner, Adam Abu-Abeid, Danit Dayan, Andrea Gat, Mor Miodovnik, Carmit Levy, Eran Nizri","doi":"10.1097/CMR.0000000000001019","DOIUrl":"10.1097/CMR.0000000000001019","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"155-161"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relation between dabrafenib plus trametinib-induced pyrexia and age in BRAF V600-mutated metastatic melanoma patients: A post hoc analysis of the real-world ELDERLYMEL study.","authors":"Inés González-Barrallo, Victoria Eugenia Castellón Rubio, Javier Medina, Sofia España Fernández, Karmele Mujika, Margarita Majem, Carlos Aguado, Miguel Ángel Cabrera Suárez, Isabel Palacio, Lisa Osterloh, Alejandro Martínez-Fernández, Almudena García-Castaño","doi":"10.1097/CMR.0000000000001020","DOIUrl":"10.1097/CMR.0000000000001020","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"170-175"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolution of diffuse cuticular melanosis under immunotherapy in a patient with metastatic melanoma.","authors":"Marie Chaveron, Elise Toulemonde, Eve Desmedt, Marie Boileau, Laurent Mortier","doi":"10.1097/CMR.0000000000001027","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001027","url":null,"abstract":"","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"35 3","pages":"213-215"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic concordance in melanoma: insights from primary tumors and their matched distant metastases.","authors":"Thamila Kerkour, Ruud W J Meijers, Loes M Hollestein, Anne M L Jansen, Ayla Haanappel, Peggy Atmodimedjo, Willeke A M Blokx, Bas van Brakel, Tamar E C Nijsten, Antien L Mooyaart","doi":"10.1097/CMR.0000000000001024","DOIUrl":"10.1097/CMR.0000000000001024","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"162-169"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain metastases during follow-up of patients with resected cutaneous melanoma.","authors":"Faruk Tas, Kayhan Erturk","doi":"10.1097/CMR.0000000000001026","DOIUrl":"10.1097/CMR.0000000000001026","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"187-191"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do cortisol and psychological distress levels impact the effectiveness of immunotherapy in patients with metastasized melanoma? A pilot study.","authors":"Chris Hinnen, Frederiek Tijssens, Emma von Haeseler, Sjoerd van de Berg, Ellen Kapiteijn","doi":"10.1097/CMR.0000000000001035","DOIUrl":"10.1097/CMR.0000000000001035","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"204-207"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffuse large B-cell lymphoma mimicking metastatic melanoma: the importance of biopsies in the era of immune checkpoint inhibitors.","authors":"Sarah Janßen, Andrew Moufarrej, Robin Springer, Lena Häberle, Paul Jäger, Christina Antke, Bernhard Homey, Harm-Henning Lindhof","doi":"10.1097/CMR.0000000000001028","DOIUrl":"10.1097/CMR.0000000000001028","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"197-200"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}