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Cancers
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Uveal Melanoma Biology, Biomarkers for Metastatic Risk and Personalized Treatment
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Uveal Melanoma Biology, Biomarkers for Metastatic Risk and Personalized Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (24 February 2024) | Viewed by 4465

Special Issue Editors

Dr. Erwin Brosens

E-Mail Website
Guest Editor
Department of Clinical Genetics, Erasmus MC Rotterdam, 3000 CA Rotterdam, The Netherlands
Interests: uveal melanoma; retinal capillary hemangioblastoma; Barrett esophagus and esophageal cancer; translational genetics; metabolomics; transcriptomics
Special Issues, Collections and Topics in MDPI journals
Dr. Emine Kilic

E-Mail Website
Guest Editor
Department of Ophthalmology, Erasmus MC Rotterdam, 3000 CA Rotterdam, The Netherlands
Interests: uveal melanoma; microRNA; genetics; prognostication; ctDNA; CTC
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There has been tremendous progress in knowledge regarding the (epi-)genomic and transcriptomic signatures of primary uveal melanoma. We can now profile these tumors up to a single cell level and provide detailed biomarker signatures. Using clinical information alongside these signatures, we can accurately classify tumors and can estimate prognosis in the range of low, mid, and high risk. We are now in the unique position of being able to explore individual patients’ germline DNA and tumor biology and provide a more detailed individual risk prediction, as well as evaluate and predict response to treatment options. Additionally, we can use this knowledge to improve our understanding of the processes behind metastasis and, for instance, develop noninvasive monitoring programs. In this Special Issue, experts in the field will contribute their science and insights into the biological mechanisms behind uveal melanoma metastasis, in vitro and in vivo experiments to elucidate uveal melanoma biology, signaling cascades to target using various interventions, and the uveal melanoma microenvironment and methods to accurately predict individual risk and treatment strategies.

Dr. Erwin Brosens
Dr. Emine Kilic
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • uveal melanoma
  • biomarkers
  • treatment
  • prognosis
  • metastasis
  • biological mechanisms
  • personalized medicine
  • molecular genetics

Published Papers (3 papers)

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Research

15 pages, 1056 KiB  
Article
Time Trends in the Treatment and Survival of 5036 Uveal Melanoma Patients in The Netherlands over a 30-Year Period
by Thaïs M. L. Tong, Esther Bastiaannet, Frank M. Speetjens, Christian U. Blank, Gregorius P. M. Luyten, Martine J. Jager, Marina Marinkovic, T. H. Khanh Vu, Coen R. N. Rasch, Carien L. Creutzberg, Jan-Willem M. Beenakker, Henk H. Hartgrink, Jacobus J. J. Bosch, Emine Kiliç, Nicole C. Naus, Serdar Yavuzyigitoglu, Caroline M. van Rij, Mark C. Burgmans and Ellen H. W. Kapiteijn
Cancers 2023, 15(22), 5419; https://doi.org/10.3390/cancers15225419 - 15 Nov 2023
Cited by 1 | Viewed by 886
Abstract
Background: Uveal melanoma (UM) is a rare intraocular tumor with a dismal prognosis once metastasized. This study provides a nationwide overview and time trends of patients diagnosed with primary UM in the Netherlands between 1989 and 2019. Methods: A retrospective population-based cohort study [...] Read more.
Background: Uveal melanoma (UM) is a rare intraocular tumor with a dismal prognosis once metastasized. This study provides a nationwide overview and time trends of patients diagnosed with primary UM in the Netherlands between 1989 and 2019. Methods: A retrospective population-based cohort study based on patients with primary UM from the database of the Netherlands Cancer Registry (NCR), linked with the national population registry Statistics Netherlands on inhabitants’ cause of death. Two time periods (1989–2004, 2005–2019) were compared with descriptive statistics. Kaplan–Meier and (multivariate) Cox proportional hazard models were used to assess changes over time for overall survival (OS) and cancer-specific survival (CSS). Results: In total, 5036 patients were analyzed with a median age of 64.0 years at the time of diagnosis. The number of patients increased over time. In the first (1989–2004) and second (2005–2019) period, 32% versus 54% of the patients received radiotherapy (p < 0.001). The median FU time was 13.4 years. The median OS of the first and second periods was 9.5 (95% CI 8.7–10.3) versus 11.3 years (95% CI 10.3–12.3; p < 0.001). The median CSS was 30.0 years (95% CI NA) in the first period and not reached in the second period (p = 0.008). In multivariate analysis (MVA), female gender (HR 0.85; 95% CI 0.79–0.92, p < 0.001) and radiotherapy treatment (HR 0.73; 95% CI 0.64–0.83, p < 0.001) were associated with better OS. Radiotherapy treatment (HR 0.74; 95% CI 0.61–0.90, p = 0.002) was also associated with better CSS. The period of diagnosis was not associated with OS or CSS. Conclusions: In this study of patients with primary UM, there was a shift to the diagnosis of smaller tumors, possibly due to stage migration. There was also an increase in eye-preserving treatments over time. OS and CSS were modestly improved in the second time period; however, the time period was not associated with OS or CSS in multivariate analyses. Full article
(This article belongs to the Special Issue Uveal Melanoma Biology, Biomarkers for Metastatic Risk and Personalized Treatment)
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12 pages, 1338 KiB  
Article
Selective Internal Radiotherapy (SIRT) and Chemosaturation Percutaneous Hepatic Perfusion (CS-PHP) for Metastasized Uveal Melanoma: A Retrospective Comparative Study
by Manuel Kolb, Andrea Forschner, Christoph Artzner, Gerd Grözinger, Ines Said, Helmut Dittmann and Ferdinand Seith
Cancers 2023, 15(20), 4942; https://doi.org/10.3390/cancers15204942 - 11 Oct 2023
Cited by 2 | Viewed by 1070
Abstract
Even with liver-targeted therapies, uveal melanoma with hepatic metastasis remains a challenge. The aim of this study was to compare the outcome of patients treated with either SIRT or CS-PHP. We included 62 patients with hepatic metastasized uveal melanoma (n = 34 with [...] Read more.
Even with liver-targeted therapies, uveal melanoma with hepatic metastasis remains a challenge. The aim of this study was to compare the outcome of patients treated with either SIRT or CS-PHP. We included 62 patients with hepatic metastasized uveal melanoma (n = 34 with SIRT, receiving 41 cycles; n = 28 with CS-PHP, receiving 56 cycles) that received their treatments between 12/2013 and 02/2020 at a single center. We evaluated their response according to the RECIST 1.1, as well as progression-free survival (PFS) and overall survival (OS), after the initiation of the first cycle of the liver-directed treatment using Cox regression, adjusted via propensity score analysis for confounders, including the amount of hepatic involvement. The disease control rate was 18% for SIRT and 30% for CS-PHP. The median (range) of PFS was 127.5 (19–1912) days for SIRT and 408.5 (3–1809) days for CS-PHP; adjusted Cox regression showed no significant difference (p = 0.090). The median (range) of OS was 300.5 (19–1912) days for SIRT and 516 (5–1836) days for CS-PHP; adjusted Cox regression showed a significant difference (p = 0.006). In our patient cohort, patients treated with CS-PHP showed a significantly longer OS than patients treated with SIRT. CS-PHP might therefore be preferable for patients with liver-dominant metastatic uveal melanoma. Full article
(This article belongs to the Special Issue Uveal Melanoma Biology, Biomarkers for Metastatic Risk and Personalized Treatment)
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16 pages, 2882 KiB  
Article
FOXD1 Is a Transcription Factor Important for Uveal Melanocyte Development and Associated with High-Risk Uveal Melanoma
by Quincy C. C. van den Bosch, Josephine Q. N. Nguyen, Tom Brands, Thierry P. P. van den Bosch, Robert M. Verdijk, Dion Paridaens, Nicole C. Naus, Annelies de Klein, Emine Kiliç and Erwin Brosens
Cancers 2022, 14(15), 3668; https://doi.org/10.3390/cancers14153668 - 28 Jul 2022
Cited by 5 | Viewed by 2018
Abstract
Uveal melanoma (UM) is a deadly ocular malignancy, originating from uveal melanocytes. Although much is known regarding prognostication in UM, the exact mechanism of metastasis is mostly unknown. Metastatic tumor cells are known to express a more stem-like RNA profile which is seen [...] Read more.
Uveal melanoma (UM) is a deadly ocular malignancy, originating from uveal melanocytes. Although much is known regarding prognostication in UM, the exact mechanism of metastasis is mostly unknown. Metastatic tumor cells are known to express a more stem-like RNA profile which is seen often in cell-specific embryonic development to induce tumor progression. Here, we identified novel transcription regulators by reanalyzing publicly available single cell RNA sequencing experiments. We identified five transcription regulators of interest: ELL2, KDM5B, REXO4, RBFOX2 and FOXD1. Our most significant finding is FOXD1, as this gene is nearly exclusively expressed in high-risk UM and its expression is associated with a poor prognosis. Even within the BAP1-mutated UM, the expression of FOXD1 is correlated with poor survival. FOXD1 is a novel factor which could potentially be involved in the metastatic capacity of high-risk UM. Elucidating the function of FOXD1 in UM could provide insight into the malignant transformation of uveal melanocytes, especially in high-risk UM. Full article
(This article belongs to the Special Issue Uveal Melanoma Biology, Biomarkers for Metastatic Risk and Personalized Treatment)
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