Uveal Melanoma (UM) is a rare disease; however, it is the most common primary intraocular malignant tumor in adults. Hematogenous metastasis, occurring in up to 50% of cases, mainly to the liver (90%), is associated with poor clinical course and treatment failure. In contrast to dramatic benefits of immunotherapy in many tumor entities, as seen in cutaneous melanoma, immune checkpoint inhibitors (ICI) do not achieve comparable results in Metastatic UM (MUM). The aim of this study was to investigate whether the combination of ICI with liver-directed therapies provides a potential survival benefit for those affected. This retrospective, single-center study, including n = 45 patients with MUM, compared the effect of combining ICI with liver-directed therapy (“Cohort 1”) with respect to standard therapies (“Cohort 2”) on overall survival (OS). Our results revealed a significant survival difference between Cohort 1 (median OS 22.5 months) and Cohort 2 (median OS 11.4 months), indicating that this combination may enhance the efficacy of immunotherapy and thus provide a survival benefit. There is an urgent need for randomized, prospective trials addressing the combination of liver-directed therapies and various strategies of immunotherapy (such as ICI; IMCgp100; personalized vaccines) in order to establish regimens which finally improve the prognosis of patients with MUM.

Background: The detection of a pathogenic variant in the BRCA1 or BRCA2 gene has medical and psychological consequences for both, affected mutation carriers and their relatives. This study analyzed the psychological impact of genetic testing and mutation-positive test result as well as associated family communication processes from the perspective of BRCA1 or BRCA2 mutation carriers and their family members.Methods: We conducted a two-phase study with explanatory sequential mixed methods design to understand the perspective of psychological process regarding genetic testing more efficiently. First, we analyzed a survey data of 79 carriers of a BRCA1 or BRCA2 mutation. Second, we conducted focus group interviews of 10 family members to deepen understanding of communication processes in high-risk families.Results: The average age of the BRCA1 or BRCA2 mutation carriers was 48 years, 58% had a history of cancer. The majority (64.6%) had general psychological distress independent of cancer diagnosis in the patients’ history. The point prevalence of depression was 16.9%. The main motives for undergoing genetic testing were desire for safety, prevention and risk assessment for the own children. The mutation carriers were satisfied with the decision to undergo genetic testing. Contrary to their subjective perception, the respondents' knowledge about those mutations was moderate. The familial communication was merely partially successful. In contrast to the high rate of disclosure to at-risk relatives (100%), the reported uptake of genetic testing among informed at-risk relatives was low (45.6%). In-depth focus group interviews with 10 family members revealed significant barriers to accessing genetic counseling including anxiety, uncertainty about the benefits of testing and the own cancer risk, particulary among males.Conclusion: The detection of a BRCA1 or BRCA2 mutation has psychological impact not only on mutation carriers but also on their family members. An adequate knowledge of the genetic background is required to reduce the level of psychological distress and to support the familial communication process. Therefore, the quality of information sources for affected individuals and relatives and also the awareness of health care professionals have to be improved.

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