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Simple Summary: In this study, we investigated whether the anatomical location of metastases from posterior uveal melanoma affects survival. We found that patients with newly diagnosed metastatic posterior uveal melanoma who only have extrahepatic metastases had a significantly longer survival compared to patients with liver metastases. This insight could help clinicians improve the prediction of patient outcomes and enhance the selection of patients in clinical trials. Background/Objectives: Metastatic posterior uveal melanoma (PUM) is one of the deadliest types of melanomas. Though the median survival is short, some patients with metastatic disease live for a long time. In this study, we investigated whether the anatomical location of the metastatic lesions is associated with differences in survival. Methods: One hundred and seventy-eight patients with metastatic PUM with baseline whole-body imaging were retrospectively included. The patients were divided into three groups based on the anatomical location of metastases: (1) exclusive liver metastases (hepatic pattern), (2) both hepatic and extrahepatic metastatic lesions (hepatic–extrahepatic pattern), and (3) exclusive extrahepatic lesions (extrahepatic pattern). Survival was investigated using Kaplan–Meier plots, log-rank test, and the Cox proportional hazard model. Results: In total, 95 patients (53%) presented with hepatic pattern, 66 patients (37%) presented with hepatic–extrahepatic pattern, and 17 patients (10%) presented with extrahepatic pattern. Overall survival was significantly longer in patients with extrahepatic pattern (median 17.0 months) compared to those with hepatic pattern (median 11.0 months) and hepatic–extrahepatic pattern (median 7.0 months) (p < 0.001, log-rank test). Multivariate Cox regression analysis showed increased hazard ratios (HR) for hepatic pattern (HR 2.37, 95% CI 1.08–5.17, p = 0.031) and hepatic–extrahepatic pattern (3.25, 95% CI 1.42–7.41, p = 0.005) compared to extrahepatic pattern. Most patients with hepatic (95%) and hepatic–extrahepatic patterns (82%) were diagnosed with metastases by liver ultrasonography screening, whereas 81% of patients with extrahepatic pattern developed symptoms that led to the diagnosis. Conclusions: Extrahepatic pattern was associated with prolonged survival in patients with metastatic PUM, despite there being a larger proportion of symptomatic patients. It is therefore important to consider the anatomical location of the metastatic lesions when stratifying patients into clinical trials. [ABSTRACT FROM AUTHOR]

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Purpose: Uveal melanoma is the most prevalent intraocular malignancy in adults, derived from uveal tract melanocytes. This study focuses on the frequency and risk of second primary malignancies in UM patients. Methods: A PubMed search (1980–2023) identified studies on SPM incidence in UM patients. From 191 references, 14 studies were chosen, focusing on UM, SPMs, and analysing data on demographics and types of neoplasms. Results: Among 31,235 UM patients in 14 studies, 4695 had 4730 SPMs (15.03% prevalence). Prostate (15%), breast (12%), and colorectal (9%) cancers were most common. Digestive system malignancies were highest (19%), with colorectal cancer leading (51%). Breast and prostate cancers were prevalent in respective systems. Lung, bladder, and non-Hodgkin's lymphoma were also notable. The study observed an increasing trend in the frequency of SPMs over time, reflecting broader trends in cancer survivorship and the growing prevalence of multiple malignancies. Conclusion: The study highlights a significant presence of SPMs in UM patients, with an increasing trend in frequency over time, emphasizing prostate and breast cancers. This underscores the need for focused surveillance and tailored follow-up for UM survivors, considering their higher risk of additional malignancies. Future research should further investigate SPM aetiology in UM patients. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is a serious condition requiring immediate medical attention. It is the most common primary intraocular cancer in adults, with an incidence of around 5.2 cases per million people annually. Nearly half of UM patients develop metastatic disease, most often affecting the liver. UM refers to any malignant tumor arising from melanocytes in the uveal tract, which includes the iris, ciliary body, and choroid. Treatment options for UM depend on several factors, including tumor size, location, and the patient's overall health. These options may include radiation therapy, surgery, laser treatments, targeted therapies, and immunotherapy. UM is often described as an immune-privileged tumor, with a distinct immune profile compared to cutaneous melanoma (CM). This article aims to highlight the unique characteristics and challenges associated with this rare form of melanoma. By providing detailed information, the article seeks to enhance understanding and management of this rare form of melanoma.

Photodynamic therapy (PDT) relies on a series of photophysical and photochemical reactions leading to cell death. While effective for various cancers, PDT has been less successful in treating pigmented melanoma due to high light absorption by melanin. Here, this limitation is addressed by 2-photon excitation of the photosensitizer (2p-PDT) using ~100 fs pulses of near-infrared laser light. A critical role of melanin in enabling rather than hindering 2p-PDT is elucidated using pigmented and non-pigmented murine melanoma clonal cell lines in vitro. The photocytotoxicities were compared between a clinical photosensitizer (Visudyne) and a porphyrin dimer (Oxdime) with ~600-fold higher σ2p value. Unexpectedly, while the 1p-PDT responses are similar in both cell lines, 2p activation is much more effective in killing pigmented than non-pigmented cells, suggesting a dominant role of melanin 2p-PDT. The potential for clinical translational is demonstrated in a conjunctival melanoma model in vivo, where complete eradication of small tumors was achieved. This work elucidates the melanin contribution in multi-photon PDT enabling significant advancement of light-based treatments that have previously been considered unsuitable in pigmented tumors. [ABSTRACT FROM AUTHOR]

Objective·To investigate the effect of F-box only protein 38 (FBXO38) on the ocular melanoma proliferation and the potential regulatory pathway.Methods·Human skin cutaneous melanoma A375 and human uveal melanoma OMM2.3 cell lines with FBXO38 knockdown and overexpression were constructed by FBXO38 short hairpin RNA (shRNA) and FBXO38 overexpression plasmids respectively. Knockdown and overexpression efficiency of FBXO38 at transcription and protein levels were verified by using quantitative real-time PCR (qRT-PCR) and Western blotting. The effects of FBXO38 on melanoma cell proliferation were detected through clonal formation assay, BrdU immunofluorescence staining and CCK8 cell proliferation assay. By using The Cancer Genome Atlas (TCGA) database, differentially expressed genes were analyzed in the high and low expression groups of FBXO38. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was performed to reveal the signaling pathways associated with FBXO38. CCK8 cell proliferation assay was used to detect the inhibition rates of the signaling pathway inhibitors on cells with different FBXO38 expression levels. qRT-PCR and Western blotting were used to detect whether the signaling pathway was activated after knocking down FBXO38.Results·qRT-PCR and Western blotting verified that mRNA and protein expression levels of FBXO38 in FBXO38 knockdown A375 and OMM2.3 cell lines decreased compared with the control group, while the expression levels of FBXO38 in the overexpression cell lines increased compared with wild type group (P

Objective: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. Methods: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. Results: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. Discussion: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals.

Objective: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. Methods: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. Results: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. Discussion: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals. [ABSTRACT FROM AUTHOR]

Objective·To investigate the effect of F-box only protein 38 (FBXO38) on the ocular melanoma proliferation and the potential regulatory pathway. Methods·Human skin cutaneous melanoma A375 and human uveal melanoma OMM2.3 cell lines with FBXO38 knockdown and overexpression were constructed by FBXO38 short hairpin RNA (shRNA) and FBXO38 overexpression plasmids respectively. Knockdown and overexpression efficiency of FBXO38 at transcription and protein levels were verified by using quantitative real-time PCR (qRT-PCR) and Western blotting. The effects of FBXO38 on melanoma cell proliferation were detected through clonal formation assay, BrdU immunofluorescence staining and CCK8 cell proliferation assay. By using The Cancer Genome Atlas (TCGA) database, differentially expressed genes were analyzed in the high and low expression groups of FBXO38. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was performed to reveal the signaling pathways associated with FBXO38. CCK8 cell proliferation assay was used to detect the inhibition rates of the signaling pathway inhibitors on cells with different FBXO38 expression levels. qRT-PCR and Western blotting were used to detect whether the signaling pathway was activated after knocking down FBXO38. Results·qRT-PCR and Western blotting verified that mRNA and protein expression levels of FBXO38 in FBXO38 knockdown A375 and OMM2.3 cell lines decreased compared with the control group, while the expression levels of FBXO38 in the overexpression cell lines increased compared with wild type group (P< 0.05). Clonal formation assay, BrdU immunofluorescence staining and CCK8 cell proliferation assay showed that FBXO38 knockdown significantly enhanced the proliferation of A375 and OMM2.3 cells (P<0.05), while overexpression of FBXO38 inhibited melanoma cell proliferation (P<0.05). Enrichment analysis showed that in skin cutaneous melanoma and uveal melanoma, FBXO38 expression influenced the phosphoinositide 3-kinase/protein kinase B (PI3K-Akt) pathway activation. Compared with those in the control group, the inhibition rates of PI3K inhibitor LY294002 and mTOR1 inhibitor Everolimus in the FBXO38 knockdown group significantly improved (P<0.05), while their inhibition rates of the overexpression group significantly decreased compared with those of control cells (P<0.05). Western blotting results showed that after knocking down FBXO38, expression levels of PTEN, P21 and P53 proteins decreased, while expression level of MDM2 protein increased. The qRT-PCR results showed a significant decrease in P53 transcription level (P<0.05) and a significant increase in MDM2 transcription level in FBXO38 knockdown cells (P<0.05). Conclusion·FBXO38 plays a role in regulating the proliferation of ocular melanoma, and this regulatory effect is related to the PI3K-Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Purpose Metastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established. Materials and Methods We retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022. Results Overall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p

Ocular melanoma stands as the predominant primary intraocular malignancy, albeit infrequently exhibiting ipsilateral inflammatory manifestations. In this article, we present an exceptional case involving a middle-aged male who presented with unilateral ocular choroidal melanoma alongside bilateral retinal vasculitis. The patient initially received temporary steroid treatment, followed by brachytherapy, which contributed to the resolution of vasculitis symptoms. The study aims to document the atypical occurrence of bilateral retinal vasculitis, which could potentially masquerade as melanoma, emphasizing the need for heightened vigilance and further investigations when encountering choroidal masses in its presence. Future research endeavors are warranted to better understand the incidence of such occurrences in this context.

A study published in the International Journal of Dermatology examines the impact of sex on the presentation and survival of conjunctival melanoma. The study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database and found that male patients had a higher incidence of the disease compared to females. Female patients, however, had higher rates of advanced disease stages and thicker tumors at the time of diagnosis. Despite this, male patients had a 45% increased risk of disease-specific mortality compared to females. The study suggests that the higher systemic availability of estrogen in females and differences in health-seeking behaviors may contribute to the survival disparities. However, the study acknowledges limitations in the database and reporting practices. [Extracted from the article]

Purpose: Metastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established. Materials and Methods: We retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022. Results: Overall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p < 0.001), higher incidence of liver metastases (89% vs. 9%, p<0.001), a lower incidence of lymph nodes metastases (16% vs. 46%, p = 0.043) and a lower incidence of BRAF mutation (0% vs. 55%, p<0.001) compared with patients with conjunctival melanoma (CM). The overall response rate of the first‐line treatment was 18%. Three of the four patients with BRAF‐mutated CM responded to dabrafenib and trametinib treatment. The median progression‐free survival (PFS) and overall survival (OS) of first‐line treatment were 5.1 and 11.9 months, respectively. Among patients with liver metastases, liver‐directed treatment was correlated with better patient PFS (p < 0.001) and OS (p < 0.001) after adjusting for number of metastatic sites and primary sites. Conclusion: CM and UM have different characteristics. Patient with CM had a high incidence of BRAF mutation, and the treatment of BRAF and MEK inhibitors conferred clinical benefit. Liver directed therapies had a potential benefit in disease control in patients with liver metastases. [ABSTRACT FROM AUTHOR]

Globally, hundreds of millions of outdoor workers are exposed to solar radiation (SR) for most of their work. Such occupational exposure is known to induce various adverse health effects on the eyes, mainly related to its ultraviolet (UV) component. The present work is a call to action to raise awareness of the need for health surveillance to prevent chronic ocular diseases in outdoor workers. Photo-chemical chronic damage can induce pterygium at the eye's outer layer and cataracts in the lens. Considering carcinogenic effects, rare squamous-cell tumors of the cornea and/or the conjunctiva and ocular melanomas are associated with UV radiation exposure. Solar UV-related eye diseases should be considered "occupational diseases" when workers have sufficient exposure. Still, they are often not recognized and/or frequently not reported to the national compensation authorities. Therefore, to prevent the burden of these workrelated eye pathologies, an adequate risk assessment with identification of appropriate preventive measures and a provision of periodic health surveillance to the exposed workers, particularly those at higher risk of exposure or with individual susceptibility, should be urgently implemented. [ABSTRACT FROM AUTHOR]

Background: In recent years, new therapeutic options to overcome the mechanisms of tumor immune suppression be effective in the treatment of cutaneous melanoma. These approaches have also been applied in ocular melanoma. The aim of this study is to present the current status and research hotspots of immunotherapy for ocular melanoma from a bibliometric perspective and to explore the field of immunotherapy for malignant ocular melanoma research. Methods: In this study, the Web of Science Core Collection database (WoSCC) and Pubmed were selected to search the literature related to immunotherapy of ocular melanoma. Using VOSviewer, CiteSpace, the R package "bibliometrix," and the bibliometric online platform through the construction and visualization of bibliometric networks, the country/region, institution, journal, author, and keywords were analyzed to predict the most recent trends in research pertaining to ocular melanoma and immunotherapy. Results: A total of 401 papers and 144 reviews related to immunotherapy of ocular melanoma were included. The United States is the main driver of research in the field, ranking first in terms of the number of publications, total citations, and H-index. The UNIVERSITY OF TEXAS SYSTEM is the most active institution, contributing the most papers. Jager, Martine is the most prolific author, and Carvajal, Richard is the most frequently cited author. CANCERS is the most published journal in the field and J CLIN ONCOL is the most cited journal. In addition to ocular melanoma and immunotherapy, the most popular keywords were "uveal melanoma" and "targeted therapy". According to keyword co-occurrence and burst analysis, uveal melanoma, immunotherapy, melanoma, metastases, bap1, tebentafusp, bioinformatics, conjunctival melanoma, immune checkpoint inhibitors, ipilimumab, pembrolizumab, and other research topics appear to be at the forefront of this field's research and have the potential to remain a hot research topic in the future. Conclusion: This is the first bibliometric study in the last 30 years to comprehensively map the knowledge structure and trends in the field of research related to ocular melanoma and immunotherapy. The results comprehensively summarize and identify research frontiers for scholars studying immunotherapy associated with ocular melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: This is the first study on the tumor microenvironment of uveal melanoma with special regard to the localization within the tumor and the eye. Uveal melanoma is the most common malignant tumor of the eye in adults. Regardless of the treatment of the primary tumor, half of the patients with uveal melanoma die due to metastasis in the long run. The major findings of this study are that blood vessels are mainly located in the middle of the tumor and that immune cells (especially CD68-immunopositive macrophages) are mostly found in the outer section of the tumor. Furthermore, this study found a high representation of lymphocyte activation gene-3 (LAG-3) and Galectin-3 in uveal melanoma. These findings could set a foundation for new therapeutic strategies aimed at improving the survival rate of patients with uveal melanoma. Uveal melanoma (UM) is a highly malignant tumor of the eye. Metastatic spread of UM occurs almost exclusively via blood vessels and is of tremendous interest, as half of the patients with uveal melanoma die of metastasis in the long run. The tumor microenvironment consists of all cellular and non-cellular compounds of a solid tumor, except for the tumor cells. This study aims to provide a more detailed understanding of the tumor microenvironment of UM to build the foundation for new therapeutic targets. Fluorescence immunohistochemistry was performed to examine the localization of various cell types in the tumor microenvironment in UM. Furthermore, the presence of LAG-3 and its ligands Galectine-3 and LSECtin was examined to evaluate the potential efficacy of immune checkpoint inhibitor-based therapies. The main findings are that blood vessels are mainly located in the middle of the tumor, and that immune cells are mostly found in the outer section of the tumor. LAG-3 and Galectine-3 were found to be highly represented, whereas LSECtin barely occurred in UM. Both the predominant location of tumor-associated macrophages in the outer section of the tumor and the high presence of LAG-3 and Galectine-3 in the UM serve as attainable therapeutic targets. [ABSTRACT FROM AUTHOR]

Purpose: The presentation of results of an ophthalmic plaque displacement as a brachytherapy treatment method of large diffuse uveal melanomas. Material and methods: This was a retrospective analysis of treatment results of 9 patients with large diffuse uveal melanomas using ophthalmic plaque displacement. Patients were treated with this method in our center between 2012 and 2021 (last follow-up visit in 2023). To achieve appropriate radiation dose distribution for large tumors with a base greater than 18 mm, brachytherapy (106Ru in 7 patients and 125I in 2 patients) with applicator displacement was used as primary treatment. Median follow-up was 2.9 years, and for patients with positive primary treatment results, it was 1.7 months. Median time to local relapse was 2.3 years. Results: In 5 patients, a positive result of local treatment was obtained, out of whom, one patient underwent enucleation due to complications. In the next 4 cases, local recurrence developed. In all tumors, the use of applicator displacement method caused that planning target volume (PTV) was effectively covered with treatment isodose. Conclusions: Brachytherapy with ocular applicator displacement allows for the treatment of tumors with base measurements larger than 18 mm. The application of this method may be considered as an alternative for eye enucleation in particular cases of large diffuse tumors, such as a neoplasm of the eye with vison, or when a patient does not consent to enucleation. [ABSTRACT FROM AUTHOR]

Background We aimed to determine the effect of clinicopathologic features on overall survival among Caucasian ocular melanoma patients in the Central Anatolia region of Turkey. Methods This single-center study included conjunctival (n = 12) and uveal (n = 19) melanoma patients diagnosed between January 2008 and March 2020. Clinicopathologic features and outcomes were reviewed retrospectively. Five cases were tested for BRAF V600 mutations with real-time polymerase chain reaction, and one case was tested with next-generation sequencing. Survival was calculated using the Kaplan-Meier method. Results Thirty-one patients had a mean initial age of 58.32 years (median, 61 years; range 25 to 78 years). There were 13 male and 18 female patients. The median follow-up time was 43.5 months (range, 6 to 155 months) for conjunctival melanoma and 35 months (range, 8 to 151 months) for uveal melanoma. When this study ended, eight of the 12 conjunctival melanoma patients (66.7%) and nine of the 19 uveal melanoma patients (47.4%) had died. The presence of tumor-infiltrating lymphocytes was related to improved overall survival in conjunctival melanoma (p = .014), whereas the presence of ulceration (p = .030), lymphovascular invasion (p = .051), tumor in the left eye (p = .012), tumor thickness of > 2 mm (p = .012), and mitotic count of >1/mm2 (p = .012) reduced the overall survival in conjunctival melanoma. Uveal melanoma tumors with the largest diameter of 9.1–15 mm led to the lowest overall survival among subgroups (p = .035). Involvement of the conjunctiva (p=.005) and lens (p = .003) diminished overall survival in uveal melanoma. BRAF V600 mutation was present in one case of conjunctival melanoma, GNAQ R183Q mutation was present in one case of uveal melanoma. Patients with uveal melanoma presented with an advanced pathological tumor stage compared to those with conjunctival melanoma (p = .019). Conclusions This study confirmed the presence of tumor-infiltrating lymphocytes as a favorable factor in conjunctival melanoma and conjunctival and lens involvement as unfavorable prognostic factors in uveal melanoma for overall survival, respectively.

MicroRNA (miRNA)-based gene therapy is a robust approach to treating human cancers. However, the low target specificity and safety issues associated with viral vectors have limited the clinical use of miRNA therapeutics. In the present study, we aimed to develop a biocompatible nanocarrier to deliver the tumor suppressor miR-30a-5p for gene therapy of ocular melanoma. The quasi-mesoporous magnetic nanospheres (MMNs) were prepared by polyelectrolytes-mediated self-assembling Fe 3 O 4 nanocrystals; the cationic polymer capped quasi-mesoporous inner tunnels of the MMNs facilitate high miRNA loading and protect from nuclease degradation. Then, the outer layer of the MMNs was modified with a disulfide bond bridged very low molecular weight polyethyleneimine (PEI) network to form redox-responsive nanospheres (rMMNs) that enhance the miRNA payload and enable miRNA release under glutathione-dominant tumor microenvironment. The miR-30a-5p loaded rMMNs nanodrug (miR-30a-5p@rMMNs) upregulated miR-30a-5p level and inhibited malignant phenotypes of ocular melanoma by targeting the transcription factor E2F7 both in vitro and in vivo. Additionally, rMMNs act as an enhancer to increase cancer cell apoptosis by modulating M1-like macrophage polarization and activating Fenton reaction. Thus, the rMMNs is a promising miRNA carrier for gene therapy and could enhance pro-inflammatory immunity in melanoma and other cancers. • miR-30a-5p@rMMNs inhibited malignant phenotypes of ocular melanoma both in vitro and in vivo. • The rMMNs promoted M1 macrophage polarization thus synergistically enhancing pro-inflammatory anti-tumor immunity against melanoma. • The rMMNs showed no obvious toxicity under the injection dose. [Display omitted] [ABSTRACT FROM AUTHOR]

The role of human oncoviruses in melanoma has been poorly investigated. The aim of this study was to investigate the association between oncoviruses and melanomas searching for human papillomavirus (HPV), Epstein Barr virus (EBV), and human herpesvirus 8DNA in melanoma specimens. Formalin‐fixed and paraffin‐embedded tissue specimens of cutaneous, mucosal, and ocular melanomas (OM) were selected from the Pathology Departments of the Galliera Hospital (Genoa) and the University Hospitals of Turin and Cagliari. Cutaneous and mucosal nevi have been collected as controls. The oncoviruses search has been performed with different polymerase chain reaction reagent kits. Fifty‐four melanomas (25 mucosal, 12 ocular, and 17 cutaneous) and 26 nevi (15 cutaneous and 11 mucosal) specimens were selected. The detection rate for one of the investigated oncoviruses was 17% in mucosal, 20% in ocular, and 0% in cutaneous melanomas (CMs). Despite the differences between groups seeming remarkable, there was no statistical significance (p > 0.5). Our data do not support a primary role of oncoviruses in melanoma carcinogenesis; however, the finding of HPV and EBV DNA in a considerable fraction of mucosal and OMs suggests that these viruses may act as cofactors in the development of extra‐CMs. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma is a rare form of melanoma but is the most common tumor in the eye. Despite having effective treatments for the initial tumor, many patients experience the spread of their cancer to distant body sites. There is no uniform way of treating metastatic disease, but physicians often use therapies that harness the patient's immune system because these same treatments have been very effective in other types of melanoma. Not all patients respond to this therapy though, and some develop toxicity related to the treatment. The goal of this paper was to identify features or blood markers that may help determine response to treatment early. Specifically, we analyzed a molecule called lactate dehydrogenase (LDH) and the ratio of different white blood cells at the start of therapy and 2 months after treatment was started. We found that these non-invasive blood markers could be useful in determining which patients are responding to treatment. Background: There is no standardized treatment for metastatic uveal melanoma (MUM) but immune checkpoint inhibitors (ICI) are increasingly used. While ICI has transformed the survival of metastatic cutaneous melanoma, MUM patients do not equally benefit. Factors known to affect ICI response include the hematologic markers, lactate dehydrogenase (LDH) and neutrophil:lymphocyte ratio (NLR). We evaluated the prognostic value of LDH and NLR at the start of ICI and on treatment in MUM. Methods: MUM patients were treated between August 2006 and May 2022 with combination ipilimumab/nivolumab or ipilimumab/nivolumab/pembrolizumab single-agent therapy. Univariable (UVA) and multivariable (MVA) analyses were used to assess the prognostic value of predefined baseline factors on progression-free (PFS) and overall survival (OS). Results: In forty-six patients with MUM treated with ICI, elevated baseline and on-treatment LDH was prognostic for OS (start of ICI, HR (95% CI): 3.6 (1.9–7.0), p < 0.01; on-treatment, HR (95% CI): 3.7 (1.6–8.8), p < 0.01) and PFS (start of ICI, (HR (95% CI): 2.8 (1.5–5.4), p < 0.0001); on-treatment LDH (HR (95% CI): 2.2 (1.1–4.3), p < 0.01). On-treatment NLR was prognostic for PFS (HR (95% CI): 1.9 (1.0–3.9), p < 0.01). On-treatment LDH remained an important contributor to survival on MVA (OS: HR (95% CI): 1.001 (1.00–1.002), p < 0.05); PFS: HR (95% CI): 1.001 (1.00–1.002), p < 0.01). Conclusions: This study demonstrates that LDH and NLR could be useful in the prognostication of MUM patients treated with ICI. Additional studies are needed to confirm the importance of these and other prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Ocular melanoma, including uveal melanoma (UM) and conjunctival melanoma (CM), is the most common ocular cancer among adults with a high rate of recurrence and poor prognosis. Loss of epigenetic homeostasis disturbed gene expression patterns, resulting in oncogenesis. Herein, we comprehensively analyzed the DNA methylation, transcriptome profiles, and corresponding clinical information of UM patients through multiple machine-learning algorithms, finding that a methylation-driven gene RBMS1 was correlated with poor clinical outcomes of UM patients. RNA-seq and single-cell RNA-seq analyses revealed that RBMS1 reflected diverse tumor microenvironments, where high RBMS1 expression marked an immune active TME. Furthermore, we found that tumor cells were identified to have the higher communication probability in RBMS1+ state. The functional enrichment analysis revealed that RBMS1 was associated with pigment granule and melanosome, participating in cell proliferation as well as apoptotic signaling pathway. Biological experiments were performed and demonstrated that the silencing of RBMS1 inhibited ocular melanoma proliferation and promoted apoptosis. Our study highlighted that RBMS1 reflects a distinct microenvironment and promotes tumor progression in ocular melanoma, contributing to the therapeutic customization and clinical decision-making. • We first demonstrated that a methylation-driven gene named RBMS1 was correlated with poor clinical outcomes. • We validated the expression level and the biological function of RBMS1 in ocular melanoma samples. • We provided evidence for the determination of an individualized therapeutic treatment for ocular melanoma patients. [ABSTRACT FROM AUTHOR]

Background: Ocular melanoma is an aggressive malignancy with a high rate of metastasis and poor prognosis. Increasing evidence indicated that DNA methylation plays an important role in the occurrence and development of ocular melanoma. Hence, exploring new diagnostic and prognostic biomarkers at the genetic level may be beneficial to the prognosis of patients with ocular melanoma. Methods: We collected DNA methylation and gene expression profiles of human UM (uveal melanoma) and CM (conjunctival melanoma) samples from various datasets. We conducted differential methylation and expression analyses to screen the potential biomarkers. Correlation analysis was performed to investigate the relationships between the expression level of DLL3 (delta-like protein 3) and the methylation level of its corresponding CpGs. We explored the prognostic and diagnostic value of DLL3 in UM and CM. Functional annotation and GSEA (gene set enrichment analysis) were applied to get insight into the possible biological roles of DLL3. A cohort of 60 ocular melanoma patients as well as UM and CM cell lines were used to validate our findings in bioinformatic analyses. Results: We found that DLL3 was a methylation-driven gene correlating with UM metastasis. The CpGs of DLL3 are mainly located in the gene body and their methylation level positively correlated to DLL3 expression. Multivariate Cox regression analysis revealed that DLL3 was an independent protective factor for UM patients. High DLL3 expression significantly prolonged the overall survival and disease-free survival of UM patients. DLL3 also showed a promising power to distinguish CM from normal tissues. Functional annotation exhibited that DLL3 may suppress UM progression through modulating immune activities and down-regulating various signaling pathways. External datasets, biospecimens, and cell lines further validated the aberrant expression and prognostic role of DLL3 in ocular melanoma. Conclusion: Methylation-driven gene DLL3 could serve as a new potential diagnostic and prognostic biomarker in ocular melanoma. Our findings may contribute to improving the clinical outcomes of patients with UM or CM. [ABSTRACT FROM AUTHOR]

Uveal melanoma is the most common malignant neoplasm of the eyeball, developing from melanocytes of the uveal membrane of the eye, which is significantly different from melanoma of the conjunctiva, mucous membranes and skin. The management of this disease is therefore different from that of other forms of melanoma. The disease is most often confined to the eye and its local treatment includes radiation therapy and surgery. Some patients, despite successful local treatment, develop distant metastases, most often located in the liver. The guidelines presented here cover the principles of diagnosis, prognostic evaluation and treatment of both the disease confined to the eyeball and the disease at the metastatic stage. The principles of management of conjunctival melanoma are also discussed. The recommen)dations are based on a review of the literature and expert opinion, and are accompanied by an assessment of their strength and reliability [ABSTRACT FROM AUTHOR]

The aim of our study is to document our cases of choroidal melanoma treated with low dose rate (LDR) brachytherapy and to correlate the dosimetry and radiobiology with clinical effects and oncologic outcomes. Data from 157 patients treated from 2014 to 2018 with LDR brachytherapy were used for this investigation. Treatments used a collaborative ocular melanoma study eye plaque and Iodine-125 radioactive seeds. The seeds activities were chosen to deliver 85 Gy to the tumor apex or to a prescription point (if the apex < 5 mm). The plaque sizes used were 10, 12, 14, 16, 18, 20, and 22 mm including notched or deep notched. The plaques were modeled in Varian BrachyVision version 11.6 (Varian Medical Systems) with seed coordinates from the AAPM Task Group 129. The Task Group 43 from AAPM was used for brachytherapy dose planning. Dose data were extracted for the apex, prescription point, sclera, retina opposite to the implant, lens, macula, and optic disc. The radiobiological dosimetry were calculated using appropriate α/β ratios found in the literature and then correlated to clinical side effects. Average biologically effective dose for associated organs at risk were calculated in cases where toxicity occurred. These included: radiation cataract (70.66 Gy), disc atrophy (475.49 Gy), foveal atrophy (263.07 Gy), radiation papillopathy (373.45 Gy), radiation maculopathy (213.62 Gy), vitreous hemorrhage (1437.68 Gy), vascular occlusion (1080.93 Gy), nonproliferative retinopathy (1066.89 Gy), proliferative retinopathy (1590.71 Gy), exudative retinal detachment (1364.32 Gy), and rhegmatogenous retinal detachment (2265.54 Gy). Average biologically effective dose was higher in patients who developed radiation induced long term side effects than in the whole patient population except for radiation maculopathy. In spite of the small patient population and short-term follow-up, it is of interest to correlate the radiation induced effects and create a guideline for the improvement of the treatment of patients treated with LDR brachytherapy. [ABSTRACT FROM AUTHOR]

Aim: This study explored uveal melanoma patient experiences and regret following molecular prognostic testing using a 15-gene expression profile (GEP) test. Materials & methods: A retrospective, cross-sectional survey study was conducted through an online questionnaire capturing patient-reported experiences with prognostic biopsy/molecular testing. Results: Of 177 respondents, 159 (90%) wanted prognostic information at diagnosis. Most 15-GEP-tested patients who shared their results (99%) reported gaining value from testing, as did patients tested with other methods. Patients who received prognostic testing experienced lower decision regret than those who opted out. Decision regret did not differ based on GEP class. Conclusion: Most uveal melanoma patients desire prognostic testing and gain value from the GEP, independent of a high- or low-risk result.

Purpose: To report a case of recurrent malignant melanoma suspected to have arisen from intrascleral melanocytic cells. Observations: En bloc removal of melanoma was performed with iridocyclectomy in a 46-year-old Caucasian male. Histopathologic examination confirmed a diagnosis of malignant melanoma in the subconjunctival space, which was presumed to have arisen from the sclera and extended both intraocularly and subconjunctivally. 15 years later, a pigmented limbal lesion near the site of the previous iridocyclectomy was excised by lamellar sclerectomy. Histopathology showed a proliferation of pigment-containing cells with atypical nuclei consistent with recurrent melanoma. Conclusions and Importance: We report a case of recurrent melanoma that we suspect arose from intrascleral melanocytes, extended both intraocularly and subconjunctivally, and recurred 15 years following initial excision.

Simple Summary: The prognosis of uveal melanoma is dependent on many factors. Among the most relevant are the tumour size, ciliary body involvement, extraocular extension, tumour cell type, genetic abnormalities, and the presence of lymphocytic infiltration. The assessment of some of these is very expensive and not available in every centre. In the search for another prognostic factor, we decided to focus on the degree of tumour pigmentation, which is very easy to assess on indirect ophthalmoscopy. It was demonstrated that patients with amelanotic uveal melanomas (those without pigment) lived longer and the eventual spread of the neoplastic process occurred later than in patients with heavily pigmented tumours. In heavily pigmented uveal melanomas, we found features on histopathological examination that were associated with an unfavourable prognosis. In the two separate groups of uveal melanomas with different degrees of pigmentation, we observed that amelanotic tumours with a lower clinical stage had the best prognosis. (1) Background: There is a constant search for new prognostic factors that would allow us to accurately determine the prognosis, select the type of treatment, and monitor the patient diagnosed with uveal melanoma in a minimally invasive and easily accessible way. Therefore, we decided to evaluate the prognostic role of its pigmentation in a clinical assessment. (2) Methods: The pigmentation of 154 uveal melanomas was assessed by indirect ophthalmoscopy. Two groups of tumours were identified: amelanotic and pigmented. The statistical relationships between these two groups and clinical, pathological parameters and the long-term survival rate were analyzed. (3) Results: There were 16.9% amelanotic tumours among all and they occurred in younger patients (p = 0.022). In pigmented melanomas, unfavourable prognostic features such as: epithelioid cells (p = 0.0013), extrascleral extension (p = 0.027), macronucleoli (p = 0.0065), and the absence of BAP1 expression (p = 0.029) were statistically more frequently observed. Kaplan–Meier analysis demonstrated significantly better overall (p = 0.017) and disease-free (p < 0.001) survival rates for patients with amelanotic tumours. However, this relationship was statistically significant for lower stage tumours (AJCC stage II), and was not present in larger and more advanced stages (AJCC stage III). (4) Conclusions: The results obtained suggested that the presence of pigmentation in uveal melanoma by indirect ophthalmoscopy was associated with a worse prognosis, compared to amelanotic lesions. These findings could be useful in the choice of therapeutic and follow-up options in the future. [ABSTRACT FROM AUTHOR]

Background. Oncology trends are based on data coming from different countries and ocular melanoma is the most common primary eye cancer in adults. Objectives. To investigate the incidence and characteristics of ocular melanoma in the overall population of Poland. Materials and methods. The retrospective survey of both the National Cancer Registry (NCR) and National Health Fund (NHF) databases was performed to identify all ocular melanoma cases in Poland in 2010-2017. Results. The mean incidence of ocular melanoma was 8.76/1,000,000 person-years; the lowest incidence was observed in the 19-29 age group (1.17/1,000,000 person-years) and the highest in the group over 70 (22.88/1,000,000 person-years). There were no statistically significant trends in the incidence rates over the study period. The overall incidences of uveal, eyelid and conjunctival melanoma were 6.67/1,000,000, 0.47/1,000,000 and 0.28/1,000,000 person-years, respectively. The 5-year overall survival (OS) was 60.76%; the higher risk of death was associated with male sex (hazard ratio (HR) = 1.2959), older age at diagnosis (HR = 1.0379), chemotherapy treatment (HR = 1.6774), metastasis (HR = 1.5716), loco-regional hyperplasia (HR = 1.5936), and systemic tumor spread (HR = 3.9872), compared to the carcinoma in situ. The risk of death was reduced by radiotherapy treatment (HR = 0.6645). Conclusions. The incidence rate of ocular melanoma in Poland is in the middle of the range worldwide, and the 5-year OS is relatively low. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is a highly malignant tumor of the eye. Metastatic spread of UM occurs almost exclusively via blood vessels and is of tremendous interest, as half of the patients with uveal melanoma die of metastasis in the long run. The tumor microenvironment consists of all cellular and non-cellular compounds of a solid tumor, except for the tumor cells. This study aims to provide a more detailed understanding of the tumor microenvironment of UM to build the foundation for new therapeutic targets. Fluorescence immunohistochemistry was performed to examine the localization of various cell types in the tumor microenvironment in UM. Furthermore, the presence of LAG-3 and its ligands Galectine-3 and LSECtin was examined to evaluate the potential efficacy of immune checkpoint inhibitor-based therapies. The main findings are that blood vessels are mainly located in the middle of the tumor, and that immune cells are mostly found in the outer section of the tumor. LAG-3 and Galectine-3 were found to be highly represented, whereas LSECtin barely occurred in UM. Both the predominant location of tumor-associated macrophages in the outer section of the tumor and the high presence of LAG-3 and Galectine-3 in the UM serve as attainable therapeutic targets.

Objective: To explore the therapeutic potential and the underlying mechanism of metformin, an adenosine monophosphate‐activated kinase (AMPK) activator, in ocular melanoma. Methods: CCK8, transwell, and colony formation assays were performed to detect the proliferation and migration ability of ocular melanoma cells. A mouse orthotopic xenograft model was built to detect ocular tumor growth in vivo. Western blot, immunofluorescence, and electron microscopy were adopted to evaluate the autophagy levels of ocular melanoma cells, and high‐throughput proteomics and CUT & Tag assays were performed to analyze the candidate for autophagy alteration. Results: Here, we revealed for the first time that a relatively low dose of metformin induced significant tumorspecific inhibition of the proliferation and migration of ocular melanoma cells both in vitro and in vivo. Intriguingly, we found that metformin significantly attenuated autophagic influx in ocular melanoma cells. Through high‐throughput proteomics analysis, we revealed that optineurin (OPTN), which is a key candidate for autophagosome formation and maturation, was significantly downregulated after metformin treatment. Moreover, excessive OPTN expression was associated with an unfavorable prognosis of patients. Most importantly, we found that a histone deacetylase, SIRT1, was significantly upregulated after AMPK activation, resulting in histone deacetylation in the OPTN promoter. Conclusions: Overall, we revealed for the first time that metformin significantly inhibited the progression of ocular melanoma, and verified that metformin acted as an autophagy inhibitor through histone deacetylation of OPTN. This study provides novel insights into metformin ‐ guided suppression of ocular melanoma and the potential mechanism underlying the dual role of metformin in autophagy regulation. [ABSTRACT FROM AUTHOR]

Aim: This meta-analysis aimed to compare the efficacy and safety of immune checkpoint blockade for the treatment of ocular melanoma. Methods: We searched the PubMed, EMBASE, and Cochrane Library databases up to July 2021. Effect sizes (ESs) and corresponding 95% confidence intervals (CIs) were used to compare the outcomes. Efficacy outcomes included complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), overall survival (OS), progression free survival (PFS). Safety outcomes included adverse events (AEs) and serious adverse event (SAEs). Results: A total of 16 eligible articles with 848 ocular melanoma patients were included. ICB treatment significantly improved CR (ES=0.02, 95%CI: 0.00-0.03, P=0.023), PR (ES=0.07, 95%CI: 0.05-0.09, P=0.000), SD (ES=0.31, 95%CI: 0.17-0.46, P=0.000), PD (ES=0.69, 95%CI: 0.61-0.77, P=0.000), ORR (ES=0.10, 95%CI: 0.04-0.15, P=0.000), OS (ES=9.68, 95%CI: 7.28-12.07, P=0.000) and PFS (ES=2.88, 95%CI: 2.69-3.07, P=0.000) in patients with ocular melanoma. Moreover, ICB therapies were associated with reduced AEs (ES=0.48, 95%CI: 0.30-0.67, P=0.000) and SAEs (ES=0.31, 95%CI: 0.18-0.45, P=0.000). Conclusions: ICB therapy showed good efficacy and safety in treating patients with ocular melanoma. [ABSTRACT FROM AUTHOR]

Abstract Objective To explore the therapeutic potential and the underlying mechanism of metformin, an adenosine monophosphate‐activated kinase (AMPK) activator, in ocular melanoma. Methods CCK8, transwell, and colony formation assays were performed to detect the proliferation and migration ability of ocular melanoma cells. A mouse orthotopic xenograft model was built to detect ocular tumor growth in vivo. Western blot, immunofluorescence, and electron microscopy were adopted to evaluate the autophagy levels of ocular melanoma cells, and high‐throughput proteomics and CUT & Tag assays were performed to analyze the candidate for autophagy alteration. Results Here, we revealed for the first time that a relatively low dose of metformin induced significant tumorspecific inhibition of the proliferation and migration of ocular melanoma cells both in vitro and in vivo. Intriguingly, we found that metformin significantly attenuated autophagic influx in ocular melanoma cells. Through high‐throughput proteomics analysis, we revealed that optineurin (OPTN), which is a key candidate for autophagosome formation and maturation, was significantly downregulated after metformin treatment. Moreover, excessive OPTN expression was associated with an unfavorable prognosis of patients. Most importantly, we found that a histone deacetylase, SIRT1, was significantly upregulated after AMPK activation, resulting in histone deacetylation in the OPTN promoter. Conclusions Overall, we revealed for the first time that metformin significantly inhibited the progression of ocular melanoma, and verified that metformin acted as an autophagy inhibitor through histone deacetylation of OPTN. This study provides novel insights into metformin ‐ guided suppression of ocular melanoma and the potential mechanism underlying the dual role of metformin in autophagy regulation.

AimThis meta-analysis aimed to compare the efficacy and safety of immune checkpoint blockade for the treatment of ocular melanoma.MethodsWe searched the PubMed, EMBASE, and Cochrane Library databases up to July 2021. Effect sizes (ESs) and corresponding 95% confidence intervals (CIs) were used to compare the outcomes. Efficacy outcomes included complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), overall survival (OS), progression free survival (PFS). Safety outcomes included adverse events (AEs) and serious adverse event (SAEs).ResultsA total of 16 eligible articles with 848 ocular melanoma patients were included. ICB treatment significantly improved CR (ES=0.02, 95%CI: 0.00-0.03, P=0.023), PR (ES=0.07, 95%CI: 0.05-0.09, P=0.000), SD (ES=0.31, 95%CI: 0.17-0.46, P=0.000), PD (ES=0.69, 95%CI: 0.61-0.77, P=0.000), ORR (ES=0.10, 95%CI: 0.04-0.15, P=0.000), OS (ES=9.68, 95%CI: 7.28-12.07, P=0.000) and PFS (ES=2.88, 95%CI: 2.69-3.07, P=0.000) in patients with ocular melanoma. Moreover, ICB therapies were associated with reduced AEs (ES=0.48, 95%CI: 0.30-0.67, P=0.000) and SAEs (ES=0.31, 95%CI: 0.18-0.45, P=0.000).ConclusionsICB therapy showed good efficacy and safety in treating patients with ocular melanoma.

Objectives: The purpose of this study is to compare genetic mutations, tumor mutation burden (TMB), and the effects of molecular targeted drugs and immune checkpoint inhibitors (ICIs) in head and neck mucosal melanoma (HNMUM) with those in skin melanoma (SKM) and ocular melanoma (OM)., Methods: Data were analyzed for 72 consecutive patients with HNMUM, including 366 with SKM and 31 with OM, registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 2019 and October 2023. Genetic alterations and TMB were determined by FoundationOne CDx next-generation sequencing., Results: The top 10 mutations in HNMUM were RAD21 (47.2%), NBN (45.8%), MYC (40.3%), LYN (31.9%), NRAS (29.1%), IRF4 (23.6%), DAXX (22.2%), KIT (22.2%), NOTCH3 (20.8%), and DDR1 (19.4%), with 16.6 ± 0.8 (mean ± SEM) mutations/individual. In SKM, BRAF (p = 0.04) mutation was associated with a significantly better prognosis. The TMB values were 5.7 ± 2.1 (mean ± SEM) in HNMUM, 4.1 ± 0.2 in SKM, and 3.4 ± 0.9 in OM, with no significant differences among the three groups. The median survival time for patients with distant metastases was 803 (95% confidence interval: 539-NA) days for HNMUM, 1413 (831-2172) days for SKM, and 1138 (438-NA) days for OM., Conclusions: The top 10 mutations in HNMUM are closer to those in OM than those in SKM. There was no significant difference in TMB values or survival rates with regard to the therapeutic effect of ICIs among the diseases, which suggests that current treatment of HNMUM with ICIs is appropriate., Level of Evidence: 3 Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: 18 F-N-(2-(Diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy) picolinamide ( 18 F-PFPN) is a novel positron emission tomography (PET) probe designed to specifically targets melanin. This study aimed to evaluate the diagnostic feasibility of 18 F-PFPN in patients with ocular or orbital melanoma., Materials and Methods: Three patients with pathologically confirmed ocular or orbital melanoma (one male, two females; age 41-59 years) were retrospectively reviewed. Each patient underwent comprehensive 18 F-PFPN and 18 F-fluorodeoxyglucose ( 18 F-FDG) PET scans. The maximum standardized uptake value (SUV max ) of the lesion and the interference caused by background tissue were compared between 18 F-PFPN and 18 F-FDG PET imaging. In addition, the effect of intrinsic pigments in the uvea and retina on the interpretation of the results was examined. The contralateral non-tumorous eye of each patient served as a control., Results: All primary tumors (3/3) were detected using 18 F-PFPN PET, while only two primary tumors were detected using 18 F-FDG PET. Within each lesion, the SUV max of 18 F-PFPN was 2.6 to 8.3 times higher than that of 18 F-FDG. Regarding the quality of PET imaging, the physiological uptake of 18 F-FDG PET in the brain and periocular tissues limited the imaging of tumors. However, 18 F-PFPN PET minimized this interference. Notably, intrinsic pigments in the uvea and retina did not cause abnormal concentrations of 18 F-PFPN, as no anomalous uptake of 18 F-PFPN was detected in the healthy contralateral eyes., Conclusion: Compared to 18 F-FDG, 18 F-PFPN demonstrated higher detection rates for ocular and orbital melanomas with minimal interference from surrounding tissues. This suggests that 18 F-PFPN could be a promising clinical diagnostic tool for distinguishing malignant melanoma from benign pigmentation in ocular and orbital melanomas., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

• New ocular plaque brachytherapy by combining COMS and BEBIG plaques. • Dual-core plque activated by IRA1-103Pd and 106Ru plate. • Dose increasement of ocular tumor relative to COMS and BEBIG plaques separately. • Reduction of exposure time for ocular beachytherapy. In recent decades, eye plaques of brachytherapy have been extensively used as primary treatment as well as a complementary treatment for ocular cancer. The purpose of this study is the development of the eye plaque brachytherapy throughout a new design of eye plaque by combining the COMS plaque and the CCB BEBIG plaque loaded by IRA1-103Pd and 106Ru, respectively. A new dual-core plaque with a diameter of 20 mm was designed in the way that the BEBIG plaque with a diameter of 20 mm loaded by 106Ru plate is attached to the COMS plaque with a diameter of 20 mm loaded by 24 of IRA1-103Pd seeds. Dose calculations for the new plaque were performed by using the MCNP5 code. Dose calculations of dual-core plaque including 103Pd seeds (gamma) and 106Ru plate (beta) were separately done for the sake of MCNP constraints in gamma and beta particle transfer simultaneously. The new dual-core plaque delivers a much higher dose rate to the tumor compared with every single plaque, while the dose rate reached to healthy tissues is slightly higher than each plaque separately. Of course, this is acceptable because the treatment time reduces and subsequently the error in radiation therapy reduces. [ABSTRACT FROM AUTHOR]

• The 106Ru plaque survey showed a large variability in terms of QA practice and image based treatment planning. • There is a large heterogeneity between the institutes regarding dose prescription and use of treatment margins. • Many responders expressed a wish to have access to calibration services, suitable QC equipment and a certified TPS. 106Ru eye plaque brachytherapy (BT, interventional radiotherapy) is an eye-preserving treatment for uveal melanoma performed in about 100 clinics worldwide. Despite this relatively low number, there is a considerable variation in clinical practice. In 2022, the BRAPHYQS and Head & Neck and Skin GEC-ESTRO working groups conducted a survey to map the current clinical practice. The survey consisted of a physicist and a physician part. This paper describes the physicist results. However, three physician questions with overlapping interest are included here as well. The survey questions pertained to commissioning and quality control (QC) of the plaques, treatment planning, radiobiological correction, as well as more general questions on practice improvement. The questions overlapping with the physician survey were related to dose prescription and margins. Sixty-five physicist responses were included. A majority of the centres do not perform an independent measurement of the absorbed dose at reference depth, percentage depth dose (PDD) and off-axis data. A lack of calibration services and suitable equipment are the main reasons. About one third of the centres indicated that they do image based treatment planning. The use of margins and dose prescription showed a large variability, despite the availability of guidelines [1]. Many respondents expressed a strong wish for improvement in a wide range of aspects of clinical practice. The physics survey showed a wide variability regarding quality control of the 106Ru sources and treatment planning practice. [ABSTRACT FROM AUTHOR]

Despite extensive research and refined therapeutic options, the survival for metastasized uveal melanoma (UM) patients has not improved significantly. UM, a malignant tumor originating from melanocytes in the uveal tract, can be asymptomatic and small tumors may be detected only during routine ophthalmic exams; making early detection and treatment difficult. UM is the result of a number of characteristic somatic alterations which are associated with prognosis. Although UM morphology and biology have been extensively studied, there are significant gaps in our understanding of the early stages of UM tumor evolution and effective treatment to prevent metastatic disease remain elusive. A better understanding of the mechanisms that enable UM cells to thrive and successfully metastasize is crucial to improve treatment efficacy and survival rates. For more than forty years, animal models have been used to investigate the biology of UM. This has led to a number of essential mechanisms and pathways involved in UM aetiology. These models have also been used to evaluate the effectiveness of various drugs and treatment protocols. Here, we provide an overview of the molecular mechanisms and pharmacological studies using mouse and zebrafish UM models. Finally, we highlight promising therapeutics and discuss future considerations using UM models such as optimal inoculation sites, use of BAP1 mut-cell lines and the rise of zebrafish models. [ABSTRACT FROM AUTHOR]