Melanoma Research最新文献

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.

Patients diagnosed with melanoma are at an elevated risk of developing subsequent primary melanomas. The aim of this study was to assess the prevalence and identify the risk factors associated with multiple primary melanomas (MPMs) in patients referred to the melanoma outpatient service of the Dermatology Unit at the University Hospital of Udine, Italy. We conducted a retrospective analysis on patients with MPMs. For each patient demographic, clinical, and histological data were collected. For each excised melanoma, we recorded Breslow thickness, histological subtype, and anatomical site. A total of 233 patients with melanoma were included in the study, comprising a subgroup of 51 (22%) patients diagnosed with MPM. The mean Breslow thickness for patients with a single melanoma was significantly higher than the Breslow thickness for the first melanoma in the MPM subgroup. Furthermore, a statistically significant decrease in Breslow thickness between the first and second melanomas was observed. In our cohort, patients with MPM had a significantly higher prevalence of nonmelanoma skin cancers (NMSCs) compared with those with a single melanoma. Our study indicates that the prevalence of MPM in the province of Udine is among the highest reported globally. Our finding aligns with the broader literature, which consistently reports lower thickness in second melanoma compared with first melanoma. Finally, the higher prevalence of NMSC in these patients suggests a potential link to chronic ultraviolet exposure.

While the association between chronic lymphocytic leukemia (CLL) and a higher incidence of melanoma is well documented, the diagnosis of concurrent high-risk chronic myelomonocytic leukemia (CMML) and metastatic melanoma (MM) has not previously been described. Moreover, the treatment of MM and CMML differ greatly in the mechanism of action of their corresponding antineoplastic therapies: treatment of MM frequently involves immune checkpoint inhibitors (ICI), while patients with CMML receive myelosuppressive agents. Simultaneous management of these malignancies can be nuanced due to the potential impact of one treatment's constituents on the activity of the other and the broad and nonoverlapping array of potential adverse effects of these agents. Here, we describe the clinical course of a patient who was diagnosed with concurrent MM and CMML and our approach to the challenging balance of delivering ICI concurrently with the hypomethylating agent azacitidine and the BCL-2 inhibitor venetoclax.

Myeloid-derived suppressor cells (MDSCs) are expanded in cancer patients, have an intrinsic immunosuppressive function, and thus may play a role in resistance to immunotherapy. Ulceration of the melanoma primary is associated with more aggressive disease and is an independent prognostic factor for melanoma-specific survival. However, the underlying factors contributing to this more aggressive phenotype are not completely understood. The current study aims to correlate changes in circulating MDSC during immunotherapy in patients with ulcerated vs non-ulcerated melanoma primary tumors. Longitudinal changes in levels of circulating MDSCs were analyzed via flow cytometry in melanoma patients receiving immune checkpoint inhibitors (ICIs) and stratified by ulceration status. Following the initiation of therapy, the percentage of total MDSCs increased significantly in patients with both ulcerated ( P  = 0.003) and non-ulcerated ( P  < 0.001) tumors. When MDSCs were stratified by subset, the proportion of granulocytic MDSC (PMN-MDSC) decreased in patients with non-ulcerated tumors ( P  = 0.023), while the proportion remained stable in patients with ulcerated tumors ( P  = 0.121). The reduction in the proportion PMN-MDSC in non-ulcerated patients coincided with a statistically significant increase in the proportion of CD14 + /CD15 + MDSC ( P  = 0.008), resulting in a greater proportion of CD14 + /CD15 + MDSC in non-ulcerated patients as compared to ulcerated melanoma patients following two infusions of ICIs (27.3 ± 19.2% vs 16.1 ± 19.2%; P  = 0.008). The trajectories of the MDSC populations described here provide insight into the altered tumor microenvironment in ulcerated melanoma and highlight key changes in a cell population that could contribute to immunotherapy resistance.

BRAF and MEK inhibitor (BRAFi + MEKi) therapy has improved the treatment of solid tumors with BRAF mutation. However, their neurologic adverse events (nAEs) have been largely unexplored. This study aimed to provide clinicians with more updated knowledge on nAEs associated with BRAFi + MEKi therapy in patients with malignant melanoma compared with nonmelanoma cancers. The United States Food and Drug Administration Adverse Event Reporting System was queried from 2011 to 2022 to capture nAEs reported for the BRAFi + MEKi therapies, vemurafenib plus cobimetinib (V + C), dabrafenib plus trametinib (D + T), and encorafenib plus binimetinib (E + B). A disproportionality analysis was performed to calculate their reporting odds ratios (RORs) and 95% confidence intervals (CIs) using a control group of antineoplastic medications. There were 2881 BRAFi + MEKi therapy-associated nAE cases, the majority of which listed malignant melanoma as the reason for use (87.5, 66.7, and 62.0% for V + C, D + T, and E + B, respectively). Several novel associations were identified; including epidural lipomatosis (ROR: 320.07, 95% CI: 123.76-827.77 for V + C), peripheral nerve lesion (ROR: 185.64, 95% CI: 73.95-466.03 for V + C), Guillain-Barre syndrome (RORs: 8.80, 2.94, and 11.79, 95% CIs: 3.65-21.22, 1.40-6.19, and 5.87-23.66 for V + C, D + T, and E + B), demyelinating polyneuropathy (RORs: 24.72 and 78.98, 95% CI: 8.16-74.86 and 24.84-251.13 for D + T and E + B), and multiple sclerosis (ROR: 5.90, 95% CI: 3.06-11.40 for D + T) in melanoma patients. nAEs in the setting of BRAFi + MEKi therapy should be a safety consideration when utilizing these medications.

Malignant melanoma is a broad and heterogeneous class of malignant tumors derived from melanocytes and classified as cutaneous (skin), uveal, and mucosal melanoma. The incidence of melanoma has increased worldwide in recent decades. Surgery remains the mainstay of treatment, but a dramatic change in systemic treatment occurred when immune checkpoint inhibitors (ICIs) entered the therapeutic armamentarium for metastatic melanoma. Pembrolizumab and nivolumab, both anti-programmed death antibodies, demonstrated superiority over standard therapies with a 5-year survival rate. Toxicities resulting from ICIs have an autoimmune etiology and can affect any organ system. We then present a case of a patient with metastatic melanoma treated with an ICI strategy who developed endocrine toxicity such as the syndrome of inappropriate antidiuresis (SIAD). A previous case report concerning an anti-programmed death ligand 1 antibody suggests that this pathway may be involved in the development of SIAD.