Up to 50% of patients with uveal melanoma develop metastatic disease with poor prognosis.,Regional, mainly liver-directed, therapies may induce limited tumor responses but do not improve overall survival.,Response rates of metastatic uveal melanoma (MUM) to systemic chemotherapy are poor.,Insights into the molecular biology of MUM recently led to investigation of new drugs.,In this study, to compare response rates of systemic treatment for MUM we searched Pubmed/Web of Knowledge databases and ASCO website (1980-2013) for “metastatic/uveal/melanoma” and “melanoma/eye.”,Forty studies (one case series, three phase I, five pilot, 22 nonrandomized, and two randomized phase II, one randomized phase III study, data of three expanded access programs, three retrospective studies) with 841 evaluable patients were included in the numeric outcome analysis.,Complete or partial remissions were observed in 39/841 patients (overall response rate [ORR] 4.6%; 95% confidence intervals [CI] 3.3-6.3%), no responses were observed in 22/40 studies.,Progression-free survival ranged from 1.8 to 7.2, median overall survival from 5.2 to 19.0 months as reported in 21/40 and 26/40 studies, respectively.,Best responses were seen for chemoimmunotherapy (ORR 10.3%; 95% CI 4.8-18.7%) though mainly in first-line patients.,Immunotherapy with ipilimumab, antiangiogenetic approaches, and kinase inhibitors have not yet proven to be superior to chemotherapy.,MEK inhibitors are currently investigated in a phase II trial with promising preliminary data.,Despite new insights into genetic and molecular background of MUM, satisfying systemic treatment approaches are currently lacking.,Study results of innovative treatment strategies are urgently awaited.,Forty clinical studies on metastatic uveal melanoma were reviewed regarding responses to systemic treatments.,New insights into genetic and molecular background led to investigation of new substances but promising in vitro data have not yet been translated into satisfying treatment responses; however, preliminary results of ongoing studies are highly encouraging.
Mucosal melanomas in the head and neck region are most frequently located in the nasal cavity and paranasal sinuses.,Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas.,The aim was to determine the KIT, NRAS and BRAF mutation frequencies in a large series of primary SNMMs.,Laser capture microdissection was used to isolate tumour cells from 56 formalin-fixed paraffin-embedded tumours.,The tumour cells were screened for KIT, NRAS and BRAF mutations by direct sequencing.,Overall, 21% (12 out of 56) of SNMMs harboured KIT, NRAS or BRAF mutations.,Mutations in these oncogenes occurred in a mutually exclusive manner.,Both KIT and BRAF mutations were identified at a similar frequency of 4% each (2 out of 56), whereas NRAS mutations were detected in 14% (8 out of 56) of the SNMMs.,Four of the NRAS mutations were located in exon 1.,Mutations in these oncogenes were significantly more common in melanomas located in the paranasal sinuses than in nasal cavity (P=0.045).,In a multivariate analysis, patients with melanomas in the nasal cavity had a significantly better overall survival than those with tumours in the paranasal sinuses (P=0.027).,Our findings show that KIT and BRAF mutations, which are accessible for present targeted therapies, are only rarely present in SNMMs, whereas NRAS mutations seem to be relatively more frequent.,The data show that majority of SNMMs harbour alterations in genes other than KIT, NRAS and BRAF.