Melanoma Research最新文献

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.

Statin use may decrease recurrence and improve survival in patients with melanoma. In this systematic review and meta-analysis, we examine the current body of literature concerning the use of statins as an adjunctive therapy in melanoma, Medline, EMBASE, CENTRAL, and PubMed were systematically searched from inception through to April 2023. Studies were included if they compared patients with melanoma receiving and not receiving statin therapy concurrently with their oncologic treatment in terms of long-term oncologic outcomes. The primary outcome was 5-year overall survival (OS). Meta-analyses was performed with DerSimonian and Laird random effects. Risk of bias was assessed with the ROBINS-I and GRADE was used to assess certainty of evidence. From 952 citations, eight non-randomized studies were identified. Included studies were conducted between 2007 and 2022. Random effects meta-analysis of adjusted hazard ratios from three studies suggested an improvement in 5-year OS with statin use with wide 95% confidence intervals (CIs) crossing the line of no effect (hazard ratio 0.87, 95% CI: 0.73-1.04, P = 0.12, I2 = 95%, very-low certainty). Outcome reporting was heterogeneous across all other oncologic outcomes such that pooling of data was not possible. Risk of bias was serious for seven studies and moderate for one study. This systematic review of studies evaluating the impact of statin use on survival in patients with melanoma found a 13% reduction in risk of death at 5 years from diagnosis - a point estimate suggesting benefit. However, the wide 95% CIs and resultant type II error risk create significant uncertainty.

Pediatric melanoma is the most common skin cancer in children and treatment relies on accurate staging. The American Academy of Dermatology recommends excisional biopsy for suspicious skin lesions, however, partial shave biopsies are often performed, the impact of which is unknown in pediatric and adolescent/young adult (AYA) patients. The aim of this retrospective case series study was to evaluate the impact of the diagnostic biopsy method on staging, treatment, and treatment-related outcomes in pediatric/AYA patients with melanoma. Among 103 pediatric/AYA patients with atypical cutaneous melanocytic lesions, the most common biopsy method was partial shave (68/103, 66.0%) followed by punch (20/103, 19.4%), excisional (14/103, 13.6%), and incisional nonshave (1/103, 1%). Over half of all biopsies yielded a positive deep margin, reflecting compromised microstaging (56/103, 55.4%), the majority occurred following partial shave (52/56, 92.9%) compared with other techniques (P < 0.001). All 11 patients with wider surgical target margins of wide local excision and 8/9 patients with sentinel lymph node biopsy performed due to positive deep margin, underwent a partial shave biopsy (P = 0.05 and 0.32, respectively). Almost half of all patients who underwent partial shave biopsy had a clinically suspected abnormal melanocytic tumor prior to biopsy (31/68, 45.6%; P = 0.03). Of 56 patients who had compromised microstaging, 17 (30.4%) had a diagnosis of melanoma (P = 0.17). Pediatric/AYA patients frequently undergo partial shave biopsy, which is associated with more invasive definitive surgical treatment due to compromised microstaging. These results may help optimize care of patients with cutaneous melanocytic tumors.

The aim of this study was to explore the epidemiology of cutaneous malignant melanoma (CMM) and the associated risk factors influencing its occurrence and survival among Koreans aged <20 years. In this retrospective cohort investigation, we identified cases of incident melanoma diagnosed in Korean patients aged 0-19 years between 2004 and 2019, utilizing the National Health Insurance database. We assessed annual fluctuations in age-adjusted incidence rates and examined 5-year survival rates based on various factors, including sex, age, income level, sun-exposed sites, and the Charlson Comorbidity Index. Of 1160 patients, 51.4% were male and 48.6% were female. The mean age of the patients was 11 years, mostly belonging to the top 25% high-income group. The head and neck regions were the most frequently affected sites. The overall age-adjusted incidence rate of melanoma was 0.22 per 100,000 persons. This rate witnessed a decline of 4.5% annually from 2004 to 2012, followed by a subsequent increase of 12.6% annually from 2012 to 2019. Notably, patients with CMM in low-sun-exposed sites exhibited poorer survival rates compared with those in high-sun-exposed areas (P < 0.05). The incidence of melanomas in children and adolescents in Korea has shown a rising trend since 2012. Further research is needed to investigate the etiology and risk factors in pediatric patients.

Melanoma is the deadliest form of skin cancer. The median age at diagnosis is 66. While most patients are treated with immunotherapy, the use of targeted therapy is a valid alternative for patients whose tumors harbor a BRAF or c-KIT driver mutation. These agents, while effective, come with a variety of side effects which limit their use, especially in older patients. We sought to assess the efficacy and toxicity of these agents in older melanoma patients. Melanoma patients over 65 treated with BRAF/MEK or c-KIT inhibitors were retrospectively identified, and their data were analyzed for treatment efficacy and toxicity. All data were compared using the Chi-square test for categorical comparisons and the Kruskal-Wallis method for median comparisons. One hundred and sixteen patients were identified. One hundred and six patients were treated with BRAF/MEK inhibitors. The assessed response rate (RR) was 83% and was comparable across different subgroups, including advanced line patients and those with a more aggressive disease. The median progression free survival (PFS) was 7.9 months, and the median overall survival (OS) was 15.7 months. Twenty-seven percent experienced grade 3-4 toxicity leading to a 24% treatment discontinuation rate. Another 10 patients were treated with the c-KIT inhibitor imatinib, for whom the assessed RR was 55%. The median PFS was 4.3 months, and the median OS was 22.6 months. Forty percent needed dose reductions, yet none had to stop treatment due to adverse effects. The use of targeted therapy in older patients is effective yet challenging due to toxicity. Deploying mitigation strategies can help maximizing their usefulness.

The aim of the study is to assess whether indocyanine green (ICG) fluorescence can replace technetium in the preoperative detection of sentinel lymph nodes (SLN) from cutaneous melanoma. The current golden standard for SLN detection is the radioisotope technetium. A promising alternative is fluorescence imaging (FLI) using ICG. In this study, we enrolled patients undergoing sentinel lymph node biopsy (SLNB) for skin melanoma at the Erasmus Medical Center between November 2022 and July 2023. The SLNB procedure was performed as a standard of care. After general anesthesia, ICG was injected intradermally around the primary tumor site. Both the patient and the surgeon were not blinded for the location of the SLN. FLI was performed before incision, in vivo after incision, and ex vivo. Fluorescent SLNs were confirmed using the gamma probe in all cases. Thirty-two patients were included in this study, and a total of 39 SLNs were harvested. The transcutaneous detection rate of ICG was 21.9%. The combined ex vivo ICG fluorescence and technetium uptake was 94.9%. One SLN contained only ICG (2.6%) and one SLN contained only technetium-uptake (2.6%). FLI using ICG resulted in a relatively low transcutaneous detection, which means that exclusive use of this technique in its present form is not feasible. However, we did find a high accumulation of ICG in the SLN, indicating the potential of ICG in combination with other imaging techniques.

Canine malignant melanoma provides a clinically relevant, large animal parallel patient population to study the GD2-reactive hu14.18-IL-2 immunocytokine as it is similar to human melanoma and expresses GD2. The objectives of this study were to evaluate safety, radiation fractionation, and identify informative biomarkers of an in-situ tumor vaccine involving local radiation therapy plus intratumoral-immunocytokine in melanoma tumor-bearing dogs. Twelve dogs (six dogs/arm) with locally advanced or metastatic melanoma were randomized to receive a single 8 Gy fraction (arm A) or three 8 Gy fractions over 1 week (arm B) to the primary site and regional lymph nodes (when clinically involved) with the single or last fraction 5 days before intratumoral-immunocytokine at 12 mg/m 2 on 3 consecutive days. Serial tumor biopsies were obtained. All 12 dogs completed protocol treatment, and none experienced significant or unexpected adverse events. Evidence of antitumor activity includes one dog with a complete response at day 60, one dog with a partial response at day 60, and four dogs with mixed responses. Histology of serial biopsies shows a variably timed increase in intratumoral lymphocytic inflammation in some dogs. Canine NanoString analyses of serial biopsies identified changes in gene signatures of innate and adaptive cell types versus baseline. There were no significant differences in NanoString results between arm A and arm B. We conclude that intratumoral-immunocytokine in combination with local radiation therapy in canine melanoma is well tolerated and has antitumor activity with the potential to inform clinical development in melanoma patients.

This meta-analysis aimed to evaluate the comparative diagnostic performance of reflectance confocal microscopy (RCM) and dermoscopy in detecting cutaneous melanoma patients. An extensive search was conducted in the PubMed and Embase databases to identify available publications up to December 2023. Studies were included if they evaluated the diagnostic performance of RCM and dermoscopy in patients with cutaneous melanoma. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. A total of 14 articles involving 2013 patients were included in the meta-analysis. The overall sensitivity of RCM was 0.94 [95% confidence interval (CI), 0.87-0.98], while the overall sensitivity of dermoscopy was 0.84 (95% CI, 0.71-0.95). These results suggested that RCM has a similar level of sensitivity compared with dermoscopy ( P  = 0.15). In contrast, the overall specificity of RCM was 0.76 (95% CI, 0.67-0.85), while the overall specificity of dermoscopy was 0.47 (95% CI, 0.31-0.63). The results indicated that RCM appears to have a higher specificity in comparison to dermoscopy ( P  < 0.01). Our meta-analysis indicates that RCM demonstrates superior specificity and similar sensitivity to dermoscopy in detecting cutaneous melanoma patients. The high heterogeneity, however, may impact the evidence of the current study, further larger sample prospective research is required to confirm these findings.

Immunotherapy has improved survival outcomes of patients with advanced melanoma. Lower gastrointestinal tract immune-related adverse events (irAEs) are common during treatment; however, gastritis is not frequently observed. Herein, we report a case of severe cytomegalovirus (CMV)-related gastritis in a patient treated with ipilimumab and nivolumab for metastatic melanoma. This report presents a 60-year-old woman with stage IV BRAF wild-type melanoma. After the second course of ipilimumab-nivolumab, the patient reported epigastric discomfort after meals, anorexia, and subsequent nausea, vomiting, epigastric pain, and weight loss. Disease staging with PET/CT scan showed very good partial response and diffuse gastroduodenitis. The patient underwent esophagogastroduodenoscopy, showing severe esophageal candidiasis and diffuse hemorrhagic, edematous, and ulcerative mucosa in the whole gastric wall. Biopsies of the gastric wall were obtained. Before receipt of the final pathology report, the patient was empirically started on corticosteroids based on the clinical suspicion of immune-related gastritis, without improvement of symptoms. The hematoxylin-eosin staining demonstrated active gastritis with diffuse nuclear cytopathic viral inclusions in epithelial and interstitial cells; CMV infection was confirmed with immunohistochemical staining. The patient started ganciclovir and fluconazole, with rapid improvement of symptoms. This case presents a rare instance of CMV gastritis in a patient receiving combined anti-PD1 and anti-CTLA4 , in the absence of immune-suppression to manage an irAE. In the case of suggestive symptoms of irAEs, a high index of clinical suspicion is required to rule out concomitant or isolated infective disease. Guidelines for prophylaxis and treatment of these patients are needed, to optimize treatment results.

Uveal melanoma is the most common intraocular tumor in adults. Our group has previously developed a human uveal melanoma animal model; however, adverse effects caused by the immunosuppressive agent, cyclosporine A, prevented animals from surviving more than 12 weeks. In this study, we tested multiple cyclosporine A doses over an extended disease course up to 20 weeks, providing complete clinical imaging of intraocular tumors, histopathological analysis and liquid biopsy biomarker analysis. Twenty albino rabbits were divided into four groups with different daily cyclosporine A schedules (0-10 mg/kg) and inoculated with human uveal melanoma cell lines, 92.1 or MP41, into the suprachoroidal space. Rabbits were monitored with fundoscopy, ultrasound and optical coherence tomography. Intraocular tumors (macroscopic or microscopic) were detected in all study animals. Tumor size and growth were correlated to cyclosporine A dose, with tumors regressing when cyclosporine A was arrested. All tumors expressed HMB-45 and MelanA; however, tumor size, pigmentation and cell morphology differed in 92.1 vs. MP41 tumors. Finally, across all groups, circulating tumor DNA from plasma and aqueous humor was detected earlier than tumor detection by imaging and correlated to tumor growth. In conclusion, using three clinically relevant imaging modalities (fundoscopy, ultrasonography and optical coherence tomography) and liquid biopsy, we were successfully able to monitor tumor progression in our rabbit xenograft model of human uveal melanoma.