Global Incidence and Trend of Uveal Melanoma from 1943-2015: A Meta-Analysis

Naseripoor, Masood; Azimi, Fatemeh; Mirshahi, Reza; Khakpoor, Golnaz; Poorhosseingholi, Asma; Chaibakhsh, Samira

doi:10.31557/apjcp.2022.23.5.1791

Cited by 10 publications

(8 citation statements)

References 46 publications

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“…The GNA11 Q209L missense mutation, giving rise to the FRMVDVGG L epitope, is the most frequent mutation in uveal melanoma (UM) (42,50% of all cases reported in TCGA). Unfortunately, the clinical impact of this neoantigen appears to be very limited because UM is a rare tumor, with an average incidence rate of 5 per million globally [ 19 ] and the binding B*27:05 and B*39:01 HLA alleles are among the least frequent in the World. The two big killers colon and stomach cancers show 18.8% and 23.9% of cases which are characterized by mutations giving rise to shared neoantigens and could benefit from cancer vaccines based on TSAs.…”

Section: Discussionmentioning

confidence: 99%

Lack of shared neoantigens in prevalent mutations in cancer

Ragone,

Cavalluzzo,

Mauriello

et al. 2024

J Transl Med

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Tumors are mostly characterized by genetic instability, as result of mutations in surveillance mechanisms, such as DNA damage checkpoint, DNA repair machinery and mitotic checkpoint. Defect in one or more of these mechanisms causes additive accumulation of mutations. Some of these mutations are drivers of transformation and are positively selected during the evolution of the cancer, giving a growth advantage on the cancer cells. If such mutations would result in mutated neoantigens, these could be actionable targets for cancer vaccines and/or adoptive cell therapies. However, the results of the present analysis show, for the first time, that the most prevalent mutations identified in human cancers do not express mutated neoantigens. The hypothesis is that this is the result of the selection operated by the immune system in the very early stages of tumor development. At that stage, the tumor cells characterized by mutations giving rise to highly antigenic non-self-mutated neoantigens would be efficiently targeted and eliminated. Consequently, the outgrowing tumor cells cannot be controlled by the immune system, with an ultimate growth advantage to form large tumors embedded in an immunosuppressive tumor microenvironment (TME). The outcome of such a negative selection operated by the immune system is that the development of off-the-shelf vaccines, based on shared mutated neoantigens, does not seem to be at hand. This finding represents the first demonstration of the key role of the immune system on shaping the tumor antigen presentation and the implication in the development of antitumor immunological strategies.

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Section: Discussionmentioning

confidence: 99%

Lack of shared neoantigens in prevalent mutations in cancer

Ragone,

Cavalluzzo,

Mauriello

et al. 2024

J Transl Med

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“…Uveal melanoma (UM) is the most frequent primary malignant ocular tumour [ 1 , 2 ] and carries a substantial risk of visual impairment and mortality due to metastatic disease [ 3 ]. UM is a rare cancer, representing 3.2% of all melanoma cases [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Incidence and Mortality of Uveal Melanoma in Hungary: A Nationwide Study

Tóth,

Muzsik,

Szajkó

et al. 2024

Cancers

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Uveal melanoma (UM) is the most common primary malignant ocular tumour in adults, although its epidemiology in Central and Eastern Europe is unclear. This study aimed to analyse the incidence and all-cause mortality of UM in Hungary. This nationwide, retrospective, longitudinal study used data from the National Health Insurance Fund and included patients aged ≥18 years who were newly diagnosed with UM (ICD-10 C69.3 or C69.4) between 1 January 2012 and 31 December 2021. Age-standardised incidence and all-cause mortality rates were calculated using European Standard Population data from 2013. We identified 88 and 70 new patients with UM in 2012 and 2021, respectively, showing an almost stable trend. Age-standardised incidence rates varied between 6.40 and 10.96/1,000,000 person-years (PYs) during the analysed period. The highest age-standardised incidence was detected among men (13.38/1,000,000 PYs) in 2015. All-cause mortality decreased from 4.72/1,000,000 PYs to 0.79/1,000,000 PYs between 2012 and 2021. In conclusion, the UM incidence rate in Hungary is comparable to European incidence rates. The incidence did not markedly change, whereas all-cause mortality decreased during the study period, but this decline could not be attributed to improved treatment modalities for primary tumours and metastatic UM.

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“…Uveal melanoma (UM) is the most common primary intraocular malignant tumour in adults, involving the iris, ciliary body or choroid, and is biologically distinct from cutaneous melanoma in terms of driver genes and mutational burden [1]. A meta-analysis of 22 studies published from 1943 to 2015 demonstrated an incidence rate of 5.74 (95% confidence interval [CI]: 4.37-7.11) and 7.30 (95% CI: 6.36-8.24) in the USA and Europe, respectively [2]. Nearly 50% of patients with UM develop metastatic disease within 15 years of their initial diagnosis.…”

Section: Introductionmentioning

confidence: 99%

A phase I trial of LXS196, a protein kinase C (PKC) inhibitor, for metastatic uveal melanoma

Piperno‐Neumann

Carlino

Boni³

et al. 2023

Br J Cancer

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Background Up to 50% of patients with uveal melanoma develop metastases (MUM) with a poor prognosis and median overall survival of approximately 1 year. Methods This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the oral protein kinase C inhibitor LXS196 in 68 patients with MUM (NCT02601378). Patients received LXS196 doses ranging from 100–1000 mg once daily (QD; n = 38) and 200–400 mg twice daily (BID; n = 30). Results First cycle dose-limiting toxicities (DLTs) were observed in 7/38 (18.4%) QD and 2/17 (11.8%) BID patients. Hypotension was the most common DLT, occurring at doses ≥500 mg/day, and manageable with LXS196 interruption and dose reduction. Median duration of exposure to LXS196 was 3.71 months (range: 1.81–15.28) for QD and 4.6 months (range: 0.33–58.32) for BID dosing. Clinical activity was observed in 6/66 (9.1%) evaluable patients achieving response (CR/PR), with a median duration of response of 10.15 months (range: 2.99–41.95); 45/66 had stable disease (SD) per RECIST v1.1. At 300 mg BID, the recommended dose for expansion, 2/18 (11.1%) evaluable patients achieved PR and 12/18 (66.7%) had SD. Conclusion These results suggest manageable toxicity and encouraging clinical activity of single-agent LXS196 in patients with MUM.

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Global Incidence and Trend of Uveal Melanoma from 1943-2015: A Meta-Analysis

Cited by 10 publications

References 46 publications

Lack of shared neoantigens in prevalent mutations in cancer

Lack of shared neoantigens in prevalent mutations in cancer

Incidence and Mortality of Uveal Melanoma in Hungary: A Nationwide Study

A phase I trial of LXS196, a protein kinase C (PKC) inhibitor, for metastatic uveal melanoma

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