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Concept: Uveal melanoma

22

To report outcomes of photodynamic therapy (PDT) as primary treatment for small amelanotic choroidal melanoma.

Concepts: Melanoma, Uveal melanoma

22

There is a gap in the recent literature on the topic of clinically misdiagnosed and unsuspected posterior uveal melanomas (PUM) with a calculation of the frequency of these events for a specific geographical area. As the only ophthalmic pathology laboratory in our region, we determined the rate of these outcomes over a 16-year period.

Concepts: Pathology, Types of cancer, Melanoma, Ophthalmology, Frequency, Uveal melanoma, Rate, Periodicity

22

About 50% of patients with choroidal melanoma develop metastatic disease, despite successful eradication of the primary tumor. Patient care is complicated by the fact that we do not know whether ocular treatment ever influences survival and if so in whom. Some authorities believe that metastatic spread is never preventable, because it has always occurred by the time the ocular tumor is detected. Others hold the view that metastatic spread can occur late, at least in some patients, in whom timely and successful treatment is life-saving. Some melanomas never seem to metastasize, even if they reach an advanced stage. It is likely that many patients are undergoing futile enucleation or experiencing severe ocular morbidity and visual loss from excessive radiation safety margins in the hope of living longer. Some of these patients would do better with tumor resection, often rejected because of concerns about iatrogenic tumor dissemination. At the same time, many patients with a small melanoma are being left untreated for years until growth is documented, possibly missing opportunities for prolonging life. Metastatic disease is highly likely when genetic tumor analysis detects monosomy 3, chromosome 8q gain, a class 2 gene expression profile, and/or BAP1 loss. Do these lethal genetic aberrations ever develop while the patient is under observation? If so, can these be predicted by genetic analysis? Do lethal mutations and metastasis ever occur because ocular treatment has failed to eradicate the tumor completely? Answers to these questions would profoundly change the management of patients with uveal melanoma.

Concepts: Gene, Cancer, Breast cancer, Metastasis, Patient, Chemotherapy, Melanoma, Uveal melanoma

22

Plaque brachytherapy remains the dominant globe-sparing therapy of uveal melanoma. This report highlights recent advances, which have expanded plaque brachytherapy’s uses as well as improved the surgical technique.

Concepts: Medicine, Surgery, Chemotherapy, Radiation therapy, Creativity techniques, Melanoma, Ophthalmology, Uveal melanoma

17

Uveal melanoma (UM) can be classified by gene expression profiling (GEP) into Class 1 (low metastatic risk) and Class 2 (high metastatic risk), the latter being strongly associated with mutational inactivation of the tumor suppressor BAP1. Nevertheless, a small percentage of Class 1 tumors give rise to metastatic disease. The purpose of this study was to identify biomarkers of metastasis in Class 1 tumors.

Concepts: Gene expression, Cancer, Metastasis, Oncology, Chemotherapy, Melanoma, DNA microarray, Uveal melanoma

6

Uveal melanoma accounts for 85% of the ocular melanomas and has an increased risk of hematogenous spread, most commonly to the liver. After curative intent therapy like surgery and radiation, fifty percent of patients present with distant metastasis. Metastatic uveal melanoma (MUM) does not harbor typically targetable mutations, e.g., BRAF as in cutaneous melanoma. As a result, there is no proven therapy for MUM. Various chemotherapy and immunotherapy regimens have been tried and only partial response (PR) is the best that has been achieved in most of the cases. Here, we present a case of MUM treated with combination immune checkpoint therapy (ipilimumab and nivolumab) following the progression with single-agent nivolumab and demonstrating a durable response without recurrence more than 22 months from the last treatment.

Concepts: Cancer, Breast cancer, Metastasis, Oncology, Chemotherapy, Radiation therapy, Melanoma, Uveal melanoma

4

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease.

Concepts: Medicine, Cancer, Metastasis, Oncology, Cure, Chemotherapy, Melanoma, Uveal melanoma

4

3

PERP (p53 apoptosis effector related to PMP-22), a transcriptional target of p53, is downregulated and contributes to the impairment of apoptosis in uveal melanoma (UM). Intriguingly, PERP is not induced in UM despite functional p53. p63, located on chromosome 3, which is characteristically altered in high-risk UM, can transactivate PERP. Here, we determine the functional role of p63 expression in the initiation of p53/PERP-mediated apoptosis in UM.

Concepts: DNA, Gene, Cancer, Transcription factor, Cell cycle, Initiation, Uveal melanoma

2

Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease. We have first carried out a meta-analysis of publicly available whole-genome datasets, that included data from 132 patients, comparing metastatic vs. non metastatic uveal melanomas, in order to identify the most relevant genes characterizing the spreading of tumor to the liver. Subsequently, the L1000CDS(2) web-based utility was used to predict small molecules and drugs targeting the metastatic uveal melanoma gene signature. The most promising drugs were found to be Cinnarizine, an anti-histaminic drug used for motion sickness, Digitoxigenin, a precursor of cardiac glycosides, and Clofazimine, a fat-soluble iminophenazine used in leprosy. In vitro and in vivo validation studies will be needed to confirm the efficacy of these molecules for the prevention and treatment of metastatic uveal melanoma.

Concepts: Cancer, Breast cancer, Metastasis, Oncology, Lung cancer, Chemotherapy, Melanoma, Uveal melanoma