Melanoma Research最新文献

Our primary objective was to estimate the overall response rate to immune checkpoint inhibitors (ICIs) in patients with locally advanced, multiply recurrent, or metastatic conjunctival melanoma treated with ICIs. A retrospective review of all consecutive conjunctival melanoma patients who were treated with ICI between October 2017 and January 2024 was carried out. The study included 16 patients with a median age of 66 years. The indications for ICI were locally extensive conjunctival melanoma in the eye/orbital area without nodal or distant metastasis in 10 patients, local recurrence of conjunctival melanoma and simultaneous nodal or distant metastasis in four patients, and metastatic conjunctival melanoma without local recurrence in two patients. Five patients received PD-1 inhibitor monotherapy with nivolumab or pembrolizumab; the other 11 received ipilimumab (CTLA-4 inhibitor) and nivolumab for several cycles and were then continued on nivolumab monotherapy ( n = 6) or not given additional ICI therapy ( n = 3). The number of cycles of ICI ranged from 2 to 25 (median, 13). Eight patients achieved a complete response. Six patients had progressive disease. The overall rate of objective response to ICI therapy was 63% (10 of 16), and for the subset of patients with local disease only, the objective response rate was 70% (7 of 10). In 14 patients (88%), orbital exenteration or additional extensive surgery was avoided; two patients had progression despite ICI and eventually needed an orbital exenteration. Future studies should aim to correlate biomarker data with response to ICI therapy in patients with conjunctival melanoma.

The management of head and neck melanoma (HNM) is constantly being fine-tuned in the era of immunotherapy. HNM have different metastatic patterns and a worse prognosis than melanoma of the trunk, asking for a more fine-tuned managing strategy. In clinically node-negative HNM patients, the ultrasound (US) with fine needle aspiration cytology (FNAC) and chest X-ray (CXR) are optional modalities in the preoperative staging workup. The contribution of imaging seems limited in this stage of disease. This study aims to research the value of the US-FNAC and CXR in clinically node-negative HNM patients. Clinical stage I-II HNM patients from 2016 to 2021 were retrospectively reviewed. A total of 373 patients were analyzed. Patient characteristics, surgery and follow-up details, recurrences, tumor characteristics, staging, imaging, sentinel node procedure (SNP) details, and lab results were collected from the patient files. All patients received preoperative US. A total of 65 FNACs were performed, which found metastatic lymph nodes in two patients (0.54%). The CXR was performed in 336/373 patients and did not find any pulmonary metastases. The SNP was performed in 242 patients and demonstrated 40 positive patients, with 86% having micrometastases, isolated tumor cells, or submicrometastases. This study demonstrated a low number of relevant findings by both the US and CXR. We can conclude that both imaging modalities do not have a significant contribution to the routine staging procedure of clinical stage I-II HNM in our study group, with our results being in line with current general melanoma guidelines.

The incidence of heart transplants in the USA has increased by 85.8% since 2011, resulting in a growing population of recipients requiring long-term immunosuppressive therapy. While essential for preventing organ rejection, this therapy significantly increases melanoma risk. This meta-analysis investigates the incidence and risk factors of melanoma in heart transplant recipients. A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including observational studies reporting melanoma incidence in heart transplant recipients. Relative risk (RR) was synthesized from standardized incidence ratios, hazard ratios, incidence rate ratios, and standardized mortality ratios. The meta-analysis incorporated 10 studies, including 22 415 heart transplant recipients. The pooled RR was 2.21 (95% confidence interval: 1.32-3.71; P  = 0.003), indicating a significantly elevated melanoma risk. This study highlights the critical need for preventive dermatological strategies in heart transplant recipients and calls for further research into the impact of different immunosuppressive regimens on melanoma risk. Despite limitations, these findings offer valuable insights for optimizing long-term patient care.

The link between palliative care and oncology must continue to develop, taking into account advances in treatment.Immune checkpoint inhibition (ICI) for metastatic melanoma is associated with different types of response, making it difficult to assess the benefits to the patient. Some clinical trials suggest a survival advantage of ICI even in the absence of an objective radiographic response. The aim of this study is to assess the impact of continuing ICI after progression of the disease on the overall survival (OS) in a cohort of final-line metastatic melanoma patients. Clinical data from 120 patients with metastatic melanoma were collected via Melbase, a French multicentric biobank, prospectively enrolling unresectable melanoma. Two groups were defined: patients continuing final-line ICI at progression (treated) and patients stopping ICI at progression (controls). The primary end-point is the OS from progression. Propensity score weighting was used to correct for indication bias. From the 120 patients, 72 (60%) continued ICI. Median OS from progression was 4.2 months [95% confidence interval (CI) 2.6-6.27] in the treated group and median OS was 1.3 months (95% CI 0.95-1.74) in the control group ( P  < 0.0001). The calculated hazard ratio was 0.20 (0.13-0.33). Continued ICI was discovered to have an association with a higher rate of hospitalization at the end of life; more treatments received in the last 15 days of life and less utilization of specialist palliative care. This study discovered that patients with metastatic melanoma show a significant decrease in the instantaneous probability of mortality when they continue with finale-line ICI after progression.

Cutaneous malignant melanoma (CMM) is one of the most aggressive and lethal types of skin cancer. Cytoskeletal remodeling is a key factor in the progression of CMM. Previous research has shown that activating transcription factor 3 (ATF3) inhibits metastasis in bladder cancer by regulating actin cytoskeleton remodeling through gelsolin. However, whether ATF3 plays a similar role in cytoskeletal remodeling in CMM cells remains unknown. Various gene and protein expression analyses were performed using techniques such as reverse transcription quantitative PCR, western blot, immunofluorescent staining, and immunohistochemical staining. CMM viability, migration, and invasion were examined through cell counting kit-8 and transwell assays. The interactions between cell division cycle 42 (CDC42) and ATF3 were investigated using chromatin immunoprecipitation and dual-luciferase reporter assays. CDC42 was upregulated in CMM tissues and cells. Cytoskeletal remodeling of CMM cells, as well as CMM cell proliferation, migration, and invasion, were inhibited by CDC42 or ATF3. ATF3 targeted the CDC42 promoter region to regulate its transcriptional activity. ATF3 suppresses cytoskeletal remodeling in CMM cells, thereby inhibiting CMM progression and metastasis through CDC42. This research may provide a foundation for using ATF3 as a therapeutic target for CMM.

Although mucosal melanomas are rare and constitute approximately 1.4% of all melanomas, the prognosis of patients with mucosal melanoma is poorer in comparison to cutaneous melanomas. Despite their poor prognosis, limited treatment options are currently available for patients with advanced disease. These noncutaneous subtypes of melanomas are not responding to treatment used for cutaneous melanomas. We performed RNA sequencing on four mucosal melanoma samples comprising of two primary tumors and two corresponding metastases. A TRIM33 :: CSDE1 fusion was detected in both the primary tumor and metastasis of a vulvar melanoma, supporting the fusion to be a driver in oncogenesis. Vulvar melanoma is the third tumor to have been reported to harbor TRIM33 :: CSDE1 fusion. Detecting fusions may have a clinically significant impact in patients with advanced mucosal melanoma who have failed front-line immunotherapy.

Melanoma is an aggressive tumor that is challenging to treat. Talimogene laherparepvec (T-VEC), the first oncolytic virus treatment approved by the US Food and Drug Administration to treat unresectable melanoma, was recently used in recurrent tumors after initial surgery. Our network meta-analysis aimed to compare T-VEC treatment of metastatic melanoma with treatment of granulocyte-macrophage colony-stimulating factor (GM-CSF) and control group. The protocol for this network meta-analysis was retrospectively registered with PROSPERO (CRD42022363321). Three databases, namely Embase, PubMed, and Cochrane Library, were searched until 10 June 2024. The search terms used were a combination of 'metastatic melanoma', 'melanoma', 'T-VEC', 'talimogene laherparepvec', and 'GM-CSF'. Seven studies, with 978 participants receiving T-VEC treatment, 649 participants receiving GM-CSF treatment, and 938 participants constituting the control group, were included in our meta-analysis. For 1-year overall survival (OS), the league table revealed significant differences between the control and T-VEC groups [0.90 (0.83, 0.99)]. The disease-free survival (DFS) over 2 years was also analyzed showing no difference between the groups in DFS in the league table. T-VEC may be a favorable treatment for metastatic melanoma owing to the notable increase in OS. Nevertheless, due to the side effects and limitations, the clinical benefits of T-VEC therapy in metastatic melanoma should be interpreted cautiously. This network meta-analysis demonstrates that T-VEC may be a favorable choice of treatment for metastatic melanoma.

Vulvar and vaginal melanomas (VVMs) are rare malignancies, but they are relatively more common among Asian women. This makes the collection of data on VVMs in this population crucial. Moreover, no cohort studies have examined and compared the effects of immune checkpoint inhibitors (ICIs) on VVM in Asian women. Therefore, we aimed to investigate the clinical characteristics of VVMs in Japanese women and the effects of ICI treatment. This single-center, retrospective cohort study included patients who were histologically diagnosed with VVM at our hospital between March 2005 and December 2023. The Kaplan-Meier analysis was used to compare the prognosis of vulvar melanoma (VuM) and vaginal melanoma (VaM) throughout entire treatments and compare the efficacies of ICIs and conventional chemotherapies in VVM. In total, 28 women with VuM ( n  = 14) and VaM ( n  = 14) were included. There were no significant differences in overall survival (OS) [median OS: not reached (95% confidence interval (CI), 13.2-NA) vs. 30.2 months (95% CI, 23.2-NA), log-rank test, P  = 0.456] between the VuM and VaM groups. The progression-free survival (median progression-free survival: 14.7 vs. 5.2 months, P  = 0.002) and OS (median OS: 33.8 vs. 7.2 months, P  < 0.001) were significantly better for the ICI-treated group than for the conventional chemotherapy-treated group in VVM. The prognosis of patients with VVM improved significantly with the advent of ICI, demonstrating the importance of ICI in the treatment of VVM.

Immunotherapy treatments that target programmed cell death receptor-1 (PD-1) or its ligand (PD-L1) have revolutionized the treatment of metastatic melanoma and currently represent the standard first-line treatment for this type of cancer. However, it is still not entirely clear which biomarkers are cost-effective, simple, and highly reliable. This systematic review and meta-analysis aims to analyze the predictive value of the baseline neutrophil-lymphocyte ratio (NLR) regarding disease progression and overall survival of patients with metastatic melanoma undergoing treatment with PD-1/PD-L1 blockade. PubMed, Scopus, and Web of Science were searched for studies comparing high versus low NLR. We performed the meta-analysis using RStudio v4.4.2 software. A total of 20 studies and 2691 patients were included, all with diagnoses of melanoma. The majority of the individuals were male 2278 (84, 65%). The median overall survival (OS) and progression-free survival (PFS) ranged from 5.0 to 44.4 and from 1.8 to 15.0 months, respectively. Compared with the high NLR ratio, the low exposure group achieved better rates of OS [hazard ratio (HR), 2.07; 95% CI, 1.73-2.48; P  < 0.00001; I ² = 47%]. Regarding PFS, there was a statistically significant difference between groups with tendencies toward the low NLR exposure group (HR, 1.59; 95% CI, 1.39-1.81; P  < 0.00001; I²=31%]. This systematic review and meta-analysis revealed significant lower OS in melanoma patients treated with PD-1/PD-L1 blockade who had elevated baseline NLR values. Furthermore, an increased PFS was observed in patients with a lower baseline NLR value. This study highlights NLR as an important prognostic biomarker for patients with metastatic melanoma who are candidates for treatment with PD-1 and PD-L1.